Impact Report

Thank you for being part of our VeloSano family.

Our primary goal is to fund cancer research, and continue to make scientific discoveries that lead to better outcomes, and, ultimately, cures. (Photo: Big Wheeler (aka Top Fundraisers) group photo at the 2019 Kickoff Party)

Projects Funded in 2020

VeloSano supports projects that will build upon and transition recent advancements in cancer research into new diagnostics and therapeutics with a high likelihood of leading to successful, future, extramural grant funding. In the first six years, VeloSano generated over $21 million which has been used to fund more than 150 cancer research projects. VeloSano 6 (2019) alone raised $4.7 million and funded the following Pilot and Impact Projects that were awarded in 2020:
 

 

Pilot Awards

The VeloSano Pilot Awards provide seed funding for cancer research activities being performed across the Cleveland Clinic enterprise. Utilizing a competitive application and peer-review selection process, the goal of the VeloSano Pilot Awards is to support projects with a high likelihood of leading to successful, future extramural grant funding. The focus of these one year grants is to build upon and transition recent advancements in cancer genetics and epigenetics and basic and translational tumor immunology.

Impact Awards

The VeloSano Impact Awards are distributed by the VeloSano Medical Chairman to satisfy the critical needs of the Cleveland Clinic cancer program. Whether a piece of equipment, advanced technology, recruitment or laboratory expenses, the VeloSano Impact Awards are to address strategic priorities that will advance the investigational abilities in the area of cancer research. These awards are meant to ensure that our caregivers and patients have access to the best talent and technology available.

2020 Award 1
Lung Cancer

Pilot Award
Lung Cancer

USP14 control of DNA damage-induced DNA repair and innate immunity in non-small cell lung cancer.

Principal Investigator

Non-small cell lung cancer (NSCLC) represents ~85% of lung cancer cases. Despite decades of research, treatments for advanced NSCLC are limited to radiotherapy (RT) alone or in combination with chemotherapy. Recently, immune checkpoint inhibitors (ICis), drugs that unleash an immune system attack on cancer cells, have fundamentally changed NSCLC treatment. However, response rates to ICis remain poor. The DNA damage response (DDR) helps a cell identify and correct damage to its DNA. Unrepaired DNA double-strand breaks (DSB) are responsible for most cell death in response to RT; therefore, identifying regulators of DSB repair could sensitize tumor cells to RT by further preventing DNA repair and thus increase tumor cell death. Moreover, recent clinical data indicate that a defective DDR predicts improved response to ICis. We have identified a novel role for the enzyme USP14 in regulating DDR and innate immune pathways in response to IR. Using NSCLC cell lines, cell line- and patient-derived tumor models in mice, we will study whether a combination of USP14 inhibition, RT, and ICis in NSCLC not only kills tumor cells by damaging their DNA, but also by attracting immune cells to attack them and enhance tumor cell death. At completion, this study will: (1) establish USP14 as a potential radiosensitizer, (2) improve understanding of how targeting DDR enhances anti-tumor immune response; (3) identify which key driver gene mutations define those NSCLC patients who are ideal candidates for targeting USP14-DDR-innate immunity. Our goal is to translate this approach to improve treatment options for NSCLC patients.

In Other Words

This project aims to find better treatments for lung cancer (NSCLC) by analyzing the role of the enzyme USP14 that we identified to have a novel role in regulating the DNA damage response and innate immune pathways in response to radiotherapy. We will study whether a combination of USP14 inhibition, radiotherapy, and immune checkpoints not only kills tumor cells by damaging their DNA, but also by attracting immune cells to attack them and enhance tumor cell death.

2020 Award 10
Blood and Marrow Transplantation, Blood Cancers

Pilot Award
Blood and Marrow Transplantation, Blood Cancers

A Pilot Study of Nicotinamide Riboside Supplementation in Allogeneic Hematopoietic Cell Transplantation.

Principal Investigator

Allogeneic transplantation using a related or unrelated bone marrow donor is a curative treatment for many life-threatening blood cancers. Donor cells can take some time to settle down (engraft) in the recipient bone marrow and occasionally may not engraft at all. Delay in engraftment can lead to prolonged hospitalization, frequent need for blood transfusions and high chance of life-threatening infections. Lack of engraftment is a life-threatening complication that my need a second transplant. Hence, efforts to speed up engraftment are critical to improving transplantation outcomes. Nicotinamide adenine dinucleotide (NAD+) is a vitamin like compound that is important for enhancing the growth of blood stem cells. Nicotinamide riboside (NR) is a direct precursor of NAD+ and it safely increases the levels of NAD+ in animals and in healthy people. We will conduct a pilot study to evaluate the safety of oral NR supplementation from 2 weeks before to 1, 2, and 3 weeks after in patients receiving allogeneic bone marrow transplant in order to investigate its effects on engraftment and recovery of bone marrow. We will also study lab markers of donor cell growth in transplant patients who do and don’t receive NR supplementation. If successful, our approach will be studied in larger clinical trials and has the potential to quicken bone marrow recovery after allogeneic bone marrow transplant and subsequently reduce the risks of complications.

In Other Words

This project aims to reduce complications of donor bone marrow transplantation for blood cancers and other blood diseases. We will investigate the use of a novel drug to promote settling down of donor stem cells (engraftment).

2020 Award 12
Bladder Cancer

Pilot Award
Bladder Cancer

A pioneer factor that drives neuroendocrine transdifferentiation: Defining the role of FOXA2 in Bladder Cancer.

Principal Investigator

Neuroendocrine cancer of the bladder (NEBC) carries a uniformly poor prognosis, which is directly coupled to an inadequate understanding of NEBC biology and a lack of reliable model systems for developing and testing effective treatments. NEBCs emerge from primary tumors (e.g., urothelial cancer (UC) of the bladder) and acquire the aggressive clinical and molecular features of neuroendocrine cancer (NEC) through a coordinated process of ‘transdifferentiation’. We have published a large-scale molecular profiling effort of human NEBCs and have developed pre-clinical models to dissect the genetic, epigenetic and metabolic determinants of transdifferentiation. This work has led to several important findings which form the scientific premise of our proposal: 1) Transdifferentiation from UC to NEBC is both a genetic and epigenetic phenomenon; 2) a NEBC transcriptomic profile precedes the morphologic features of NEBC and confers a poor prognosis; and 3) FOXA2, a forkhead class developmental pioneer factor which binds collapsed chromatin to activate transcription and initiate cell fate transitions, is highly upregulated in human tumors and murine models of NEBC.  In this pilot study, we will explore the pathologic role of FOXA2 in neuroendocrine transdifferentiation using patient tissues as well as innovative model systems developed in our lab. This work will expand our understanding of NEBC evolution and may uncover new therapeutic strategies for detection and treatment of the neuroendocrine subtype.

In Other Words

Cancers have subtypes which range from benign to highly aggressive -- understanding how tumors transition between these subtypes is a critical unmet need. Our lab studies the mechanisms that give rise to a deadly small cell (neuroendocrine) subtype. In this VeloSano supported project, we use a unique engineered mouse model to explore the role of a 'pioneer' transcription factor, FOXA2, in the evolution of neuroendocrine carcinoma of the bladder.

2020 Award 13
Gynecologic Cancers

Pilot Award
Gynecologic Cancers

Epithelial Ovarian Cancer Growth and Sensitivity to Cisplatin Modulation by Microbiome

Principal Investigator

Patients with epithelial ovarian cancer exhibit the poorest outcome of gynecologic cancers with overall survival of around 2 years. During cancer treatment, patients are often given antibiotics for infections with unknown impact on patient outcomes. It is now well appreciated that the microbiome impacts human health and disease. The use of broad spectrum antibiotics can lead to dysbiosis or a microbial imbalance. Using mouse models of ovarian cancer, we determined that antibiotic treatment leads to faster growth of the tumors and reduced response to chemotherapy. Tumors that grew in antibiotic treated mice, exhibited increased number of tumor initiating cells. These cells are also known to exhibit reduced response to chemotherapy. The findings lead us to hypothesize that antibiotic use can impact tumor growth by altering the microbiome. To address this question, we propose to test (1) the role of the microbiome using germ free mice and (2) the role of clinically used antibiotics.
The significance of these studies may have wide impact on use of antibiotics in clinical management of ovarian cancer patients. Improved understanding of antibiotics used in the clinical may guide future clinical practice.

In Other Words

This project aims to define the impact of antibiotics on microbiome and ovarian cancer growth and sensitivity to chemotherapy. We will determine the types of antibiotics and impact of select antibiotics on tumor growth and chemosensitivity to cisplatin. The outcomes will have the potential guide future treatment strategies for epithelial ovarian cancer patients.

2020 Award 14
Sarcoma - Epithelioid Hemangioendothelioma

Pilot Award
Sarcoma - Epithelioid Hemangioendothelioma

Characterization of a Genetically Engineered Mouse Model of Epithelioid Hemangioendothelioma

Principal Investigator

Epithelioid hemangioendothelioma (EHE) is a rare vascular cancer that is highly lethal and has no treatment. We previously discovered a genetic mutation that activates a protein (TAZ) that is specific for and absolutely crucial to EHE.  The most significant barrier to progress in the study of EHE has been the lack of a living, biological model of EHE. We have recently achieved a major breakthrough with the development of a genetically engineered mouse model (GEMM) of EHE, a true living EHE model. We did this by replacing normal TAZ in the DNA of mice with the mutated form of TAZ that causes EHE. Moreover, we engineered the mouse so that mutated TAZ is only present in vascular cells. As a result, it appears that almost all mice with mutated TAZ develop EHE. This EHE GEMM can be used to produce a limitless supply of EHE’s.  It is the purpose of this proposal to completely and thoroughly credential this EHE GEMM by comprehensively studying clinical, microscopic, and genetic attributes of GEMM EHE’s. Furthermore, we will develop derivative models that are created by growing the cells of the GEMM EHE’s in petri dishes. Success of this proposal means that we will have fully credentialed an EHE GEMM and developed derivative cell models. Since TAZ is activated in many cancers, this EHE GEMM will be useful for the study of many types of cancer that are dependent on activated TAZ.

In Other Words

This project aims to perform a detailed characterization of the first biological model of a rare vascular cancer known as epithelioid hemangioendothelioma (EHE). This model will be very useful in understanding the biology of and finding cures for this rare cancer that currently has no effective therapies.

2020 Award 15
Prostate Cancer

Pilot Award
Prostate Cancer

Targeting a Novel Epigenetic Axis to Overcome Enzalutamide Resistance in Castration-Resistant Prostate Cancer.

Principal Investigator

Next-generation androgen receptor (AR) antagonists are now a mainstay therapy for the treatment of advanced prostate cancer.  The most widely used such drug is enzalutamide.  Unfortunately, the tumor cells almost always eventually become resistant to enzalutamide.  Mechanisms that engender enzalutamide resistance include epigenetic perturbations, which are generally often involved in cancer progression.  Epigenetic changes are frequently driven by machinery in the cell nucleus that modifies histone proteins on the DNA. The overall objectives of this proposal are to use an approach where we first look at the prostate tumor cell phenotype for clues to 1) identify epigenetic drivers of enzalutamide resistance, and 2) elucidate the underlying mechanisms in order to determine new potential pharmacologic targets for therapy. Enzalutamide resistance is a major clinical issue in prostate cancer and eventually leads to patient death.  Epigenetic mechanisms of resistance may spur the development of prostate cancer that acts independently of the AR, as well as tumors that rely on glucocorticoid receptor and accompanying metabolic mechanisms of resistance.  Specific aim 1: Determine the role of H3K9 methylation-regulating machinery in progression to enzalutamide resistance. Specific aim 2: Characterize the genomic localizations of the H3K9me2/3 marks in enzalutamide-resistant cells and identify the H3K9 methylation-guided downstream cellular pathways.

In Other Words

This proposal is focused on identifying how prostate cancer resists powerful androgen blocking drugs.  We anticipate that the identification of the tumor cell circuitry that drives resistance will lead to new insights and more effective therapies.

2020 Award 16
Uveal Melanoma

Pilot Award
Uveal Melanoma

Molecularly Targeted Approaches for Metastatic Uveal Melanoma.

Principal Investigator

Uveal melanoma (UM) is the most common adult primary eye cancer. In more than 50% of patients, however, metastatic disease manifests in 10 years. Defects in DNA including a gene called SF3B1 have been associated with the risk of developing metastasis. To date no specific medicines are available for patients with UM developing metastases and defects in SF3B1. The discovery of medicines blocking the growth of cells with defects in SF3B1 will help doctors to give novel alternative treatments for patients with UM. We have produced two medicines (dihydropyridine- and thiazole-derivatives) inhibiting the growth of cells carrying SF3B1 alterations and we plan to test them in UM.

In Other Words

To improve the treatment of metastatic uveal melanoma by using molecular targeted therapy.

2020 Award 17
Colon Cancer and All Cancers

Pilot Award
Colon Cancer and All Cancers

Discovering the origin of cancer epimutation.

Principal Investigator

In addition to disruptions to the genetic material (DNA), cancer cells also harbor epigenetic aberrations. DNA methylation is a form of epigenetic modification, which changes the biochemical properties of DNA without changing the actual DNA sequence. Striking, genome-wide differences in DNA methylation exist between normal and cancer tissues and hold valuable information about what makes cancer deadly. For example, cancer-associated, abnormal DNA methylation can inappropriately shut off caretaker genes that otherwise prevent cancer formation and can also inappropriately turn on growth-promoting genes that fuel cancer development. While we have substantial knowledge of the location and function of abnormal DNA methylation across tumor types, we are woefully naïve about how such abnormality is established during cancer formation. Without such knowledge, we cannot begin to evaluate if preventing abnormal DNA methylation is possible or a viable cancer prevention/treatment strategy. Trillions of bacteria live in/on our body, closely interact with human cells, and impact our health. More than 90% of these commensal microorganisms can methylate their own DNA, and they do so to protect their genome against other microbes. Certain bacteria in the gut has been found to invade human cells and are potentially linked to colon cancer development. Here we propose to investigate a brand-new concept where gut bacterial defense enzymes, called DNA methyltransferases, can enter into the human cell and cause abnormal DNA methylation in colon cancer. If successful, we will uncover a novel host-microbe interaction that may be targeted for disruption in cancer prevention and treatment.

In Other Words

This project aims to find the cause of abnormal DNA methylation in colorectal cancers. We hope to use this information to prevent this from happening and in doing so, develop a potential colon cancer prevention strategy.

2020 Award 18
All Cancers

Impact Award
All Cancers

Genomic Sequencing to Identify Clonal Hematopoiesis

Principal Investigator

Clonal hematopoiesis is an age-associated disorder found in healthy individuals and in patients with solid tumor malignancies marked by expansion of hematopoietic clones carrying recurrent somatic mutations found commonly in myeloid malignancies. The identification of clonal hematopoiesis has been described to increase the risk of subsequent blood cancer and risk for cardiovascular disease. With precision medicine evolving in the field of hematology/oncology, cancer survivors are living longer and there may be an increase prevalence of clonal hematopoiesis. The hypothesis of this study is that there are mutations that may increase the risk of developing blood cancers and cardiovascular disease. Early detection in patients with solid tumor malignancies, will allow for the identification of clonal hematopoiesis, development of clinical trials for early intervention, and guidelines for management.

In Other Words

This projects aims to evaluate the prevalence of clonal hematopoiesis on the peripheral blood, bone marrow, and/or surgical specimen in the upfront clinical setting and survivorship clinic using next generation sequencing panel annually. Identification of clonal hematopoiesis will allow us to evaluate clinical outcomes such as incidence of hematological malignancy, cardiovascular events( i.e. myocardial infraction, congestive heart failure), deep vein thrombosis, CVA, survival, and the role of preventive cardiology.

2020 Award 2
Liver Cancer

Pilot Award
Liver Cancer

Investigation of a novel pathway and potential therapeutic target in hepatocellular carcinoma (HCC)

Principal Investigator

This project aims to find better treatment for hepatocellular cancer (HCC), the commonest liver cancer. Its incidence is growing steadily, especially in developed countries and it is one of the deadliest cancers worldwide. Not all HCCs behave the same way clinically or respond similarly to treatments. HCC typically arises in diseased livers, e.g., those with hepatitis B or C infection or alcoholic liver disease. Although these known predisposing conditions lead to screening for HCC, it is a paradox that early diagnosis is not always achieved. The perils of late diagnoses are compounded by limited efficacy of treatments against advanced-stage HCC, which use the receptor tyrosine kinase inhibitors (RTKIs) Sorafenib and Lenvatinib.  These drugs are expensive, inconsistently efficacious and have many adverse effects. Therefore, it would be desirable to fully understand the molecular pathways that lead to HCC, find new biomarkers, in particular, those that assist patient selection for RTKI treatment, and identify new drug targets. Here, we propose that investigation of a molecule named ADAMTSL5, which we discovered to have a strong association with HCC, may help in achieving these goals. Our studies to date show that it is present in over half of HCC cases and analysis in mice shows that more ADAMTSL5 leads to larger tumors. Conversely, reducing ADAMTSL5 slows tumor growth. How it acts is not understood. We propose to define the molecular framework in which ADAMTSL5 works, particularly with reference to the RTKI targets, and seek clinical correlates of high ADAMTSL5 in HCC patients.

In Other Words

This project aims to find better treatment for hepatocellular cancer (HCC), the commonest liver cancer. Its incidence is growing steadily, especially in developed countries and it is one of the deadliest cancers worldwide.We propose to define the molecular framework in which an HCC-associated protein, ADAMTSL5, works, particularly with reference to drug targets, and seek clinical correlates of high ADAMTSL5 in HCC patients.

2020 Award 20
Multiple Myeloma, a Type of Blood Cancer

Impact Award
Multiple Myeloma, a Type of Blood Cancer

Prediction Markers and Resistance Mechanisms of BCMA targeting Treatments in Multiple Myeloma.

Principal Investigator

At the Cleveland Clinic, a large group of patients with Multiple Myeloma are managed under the care of a dedicated team of specialists. Currently no curative treatment is available, but many effective treatments are available to control Myeloma. After initial good response, many patients face the challenge of drug resistance, there is tremendous need to study the mechanism of resistance, identify markers to predict patients at risk of resistance, disease progression and develop new ways to overcome the resistance to improve treatment for Myeloma patients. Our team of physicians and laboratory scientists are working together to understand cellular mechanisms, how and why cells stop responding to very effective and targeted immunotherapy. On one hand, we want to study this issue of drug resistance by using lab cultured cell lines, lab animal to test new ways to overcome resistance, and on the other hand we will use actual patient samples, collected before and after resistance to identify the markers for resistance.  For this project, we will study a target protein called B-cell maturation antigen (BCMA) and early phase drug development trails have identified many new effective treatments against. We want to study resistance mechanism for BCMA target and hope to use the knowledge to overcome resistance, identify patients at risk of not good response, and further study similar issues facing drugs used for the targeted therapy against myeloma such as Daratumumab, Elutuzomab, Isatuximab and Cell based targeted therapies against myeloma.

In Other Words

This project aims to find better treatment for a blood cancer called Multiple Myeloma. We aim to study the mechanisms of treatment failure for Myeloma. We aim to improve treatment by overcoming resistance against Myeloma drugs.

2020 Award 22
Melanoma

Impact Award
Melanoma

Novel preventive approaches to halt and potentially reverse rapid rise in melanoma.

Principal Investigator

Melanoma incidence rates have risen over 12 fold in the last half-century, despite significant public health efforts to reduce ultraviolet radiation exposure, the best characterized environmental risk factor. Therefore, new preventive methods are necessary to halt this rapid increase in melanoma. Through the use of targeted cancer panel screening, whole exome & whole genome sequencing we propose to further characterize and/or identify novel genetic risk factors for melanoma. We will correlate this with functional laboratory work examining individual genes to better interrogate their role in melanoma. Using this functional understanding of how a specific gene is responsible for melanoma development, we will design novel preventive therapies to be used in these high risk melanoma individuals.

In Other Words

By focusing on patients at extremely high risk for melanoma, where previous work has been generalizable to early sporadic (non-familial) melanoma development, we plan to uncover novel genetic mechanisms in these individuals that are likely acquired early in melanoma initiation. These genetic changes can then be targeted in new preventive approaches.

2020 Award 23
Pediatric Sarcomas

Pilot Award
Pediatric Sarcomas

Phase 1 trial of disulfiram Combined with Gemcitabine/Docetaxel or Continuous Infusion Ifosfamide for Relalpsed and Refractory Sarcomas in Children and Young Adults.

Principal Investigator

High expression of the enzyme aldehyde dehydrogenase (ALDH) in sarcomas correlates with aggressive disease and resistance to chemotherapy drugs used to treat these cancers. Reducing ALDH levels reverses this resistance. disulfiram (Antabuse) is an inhibitor of ALDH that has been used safely for over 60 years for the treatment of alcoholism. Several pre-clinical and clinical trials have demonstrated an anti-cancer effect of disulfiram, which is enhanced when given with copper, and its ability to make tumors more sensitive to chemotherapy. We propose a clinical trial of disulfiram/copper in combination with liposomal-doxorubicin in children and young adults with relapsed/refractory sarcomas. We base this combination on published research showing inhibition of ALDH is toxic to sarcoma cells and makes them more sensitive to the chemotherapy drug doxorubicin. Many relapsed sarcoma patients have already been treated with conventional doxorubicin, but we have shown safety and renewed tumor sensitivity when administering liposomal-doxorubicin in heavily pre-treated patients including those who previously received regular doxorubicin. We will also conduct studies on the tumors to determine if ALDH expression can predict who will respond to these treatments. This trial will establish the feasibility and safety of treating relapsed sarcoma patients with disulfiram/copper and liposomal-doxorubicin and the preliminary information on the efficacy of this combination will support an expanded national study of these drugs. Our goal is to make chemotherapy more effective at eliminating the resistant cells present in sarcomas, which in turn will lead to less toxic, more effective therapies to cure these patients.

In Other Words

This trial will re-purpose the drug disulfiram to overcome the resistance to chemotherapy seen in pediatric sarcomas. Overcoming this resistance can significantly improve the cure rate for children affected by these cancers.

2020 Award 24
Ewing Sarcoma

Pilot Award
Ewing Sarcoma

Developing more effective therapy for Ewing sarcoma.

Principal Investigator

Ewing sarcoma is one of the most common and lethal pediatric cancers. Five year survival for those with metastatic disease is less than 30%. In contrast to major advances in most of the other pediatric cancers, a five-drug cytotoxic regimen has been the mainstay for its treatment for the past three decades. Also used to treat these sarcomas are surgery and radiation therapy, which may be disfiguring or carry significant morbidity. Current therapies may also contribute to the increased incidence of second malignancies in survivors of Ewing sarcoma.  Thus, there is a great need for more effective, less toxic therapies. One major obstacle to progress is the paucity of animal models. Our goal is to develop zebrafish models for Ewing sarcoma that will provide new insights into the pathogenesis and develop new therapies that will improve survival. Fish have multiple advantages to mice: 1) The fish develop within several days and are transparent; 2) Cancers develop faster in fish than mice; 3) Fish can be genetically manipulated more easily and quickly; 4) Transplants of patient-derived cancer can occur in an animal that is not deficient in cancer-fighting white blood cells; 5) Drugs can be more easily administered; and 6) The costs are significantly less. Here, I will make fish that carry the genetic changes associated with Ewing sarcoma. I will also optimize the techniques to engraft patient-derived Ewing sarcoma cells in immunocompetent zebrafish. These novel studies are feasible within one year of VeloSano funding.

In Other Words

This project aims to develop a zebrafish model to study Ewing sarcoma. This model will be useful for identifying novel mechanisms   of Ewing sarcoma progression and for development of new anticancer compounds in a time- and cost-effective manner.

2020 Award 3
Breast Cancer and Brain Cancer

Pilot Award
Breast Cancer and Brain Cancer

To Identify Targetable Modulators of Hypoxia-driven Dedifferentiation Programs using CRISPR/Cas9-based Forward Genetic Screens.

Principal Investigator

Rapidly dividing cancer cells in (non-blood) solid tumors, such as breast, brain, kidney, etc., routinely outgrow their blood supply. This reduced blood supply limits oxygen delivery and forces cancer cells to grow under oxygen-poor (or hypoxic) conditions. Hypoxic conditions impose immense stress on cancer cells, and causes them to turn on adaptive programs that compensate for (or limit) the damage caused by oxygen-deficiency. We hypothesize that such adaptive programs are vulnerabilities in tumor cells, which can be therapeutically exploited. 
Recently, for example, we discovered that hypoxia influences the “cellular identity” of cancer cells. Unlike “differentiated” normal cells, which are programmed to function as blood cells, muscle cells, neurons, or nephrons; cancer cells lose cellular identity and become “de-differentiated”. We found that oxygen loss reinforces this “de-differentiation” program, and pushes cancer cells into a “de-differentiated”, “stem-cell” like, state. These “de-differentiated” cancer stem cells are poorly responsive to anti-cancer treatments and are known to seed (metastatic) secondary drug-resistant tumors. Therefore, hypoxic “de-differentiation” programs are central to both drug-resistance and metastasis – arguably, the two major problems in cancer therapy. 
Here, using breast and glioma (brain) cancer cells, we will study how hypoxia drives such “de-differentiation” programs. Using unbiased approaches (e.g.: CRISPR/Cas9 editing, which allows us to study the effects of inactivating thousands of genes simultaneously), we will seek candidate genes whose loss can reverse hypoxia-induced “de-differentiation” programs. From a public health perspective, targeting candidates whose loss overcomes hypoxic “de-differentiation” programs, would improve response, and justify further studies on these candidates as anti-cancer targets.

In Other Words

Limited oxygen availability (or hypoxia) promotes widespread changes in a cancer cell's physiology and reverts these cells to a more drug-resistant, "stem-cell" like state. By exploiting recent technological developments (such as CRISPR/Cas9 tools), this project aims to improve cancer treatment by finding ways to eliminate these hypoxic "stem-like" cancer cells.


2020 Award 4
Glioblastoma (GBM)

Pilot Award
Glioblastoma (GBM)

A network medicine approach to identify immunotherapy resistance mechanisms in glioblastoma.

Principal Investigator

Enhancing immune cell activation to kill tumor cells via immune checkpoint inhibitors is a promising strategy for advanced cancers, including glioblastoma (GBM), a highly aggressive brain tumor. However, only a small fraction of GBM patients have a long-term response to these immunotherapies, and the molecular determinants underlying their resistance remain unclear. Our preliminary data revealed that myeloid-derived suppressor cells (MDSCs), which suppress natural killer cells and cytotoxic T lymphocytes, are elevated in GBM patients and associated with poor survival. However, the pathways leading to the accumulation of MDSCs in these patients and conferring therapeutic resistance have yet to be determined. Our recent studies demonstrate the potential of using network medicine approaches rather than traditional bioinformatics analysis to rapidly develop personalized cancer therapies. Our goal is to integrate our expertise to utilize single-cell RNA sequencing data from immunotherapy responders and non-responders as part of an ongoing immune checkpoint inhibitor clinical trial (nivolumab) to identify resistance mechanisms by examining gene regulatory networks that are changed upon treatment and other potential drug combinations to enhance immune checkpoint inhibitor efficacy in GBM. We hypothesize that systematic identification and characterization of single-cell gene regulatory networks altered by nivolumab could facilitate molecularly targeted immunotherapeutic development for GBM. Specifically, we plan to incorporate our multi-omics data from patients with public drug-target databases and the human protein-protein interactome to functionally validate these findings in well-established mouse glioma models. The successful completion of this project will identify 2-3 highly repurposable drugs or drug combinations for overcoming immunotherapy resistance.

In Other Words

This project aims to improve immunotherapy outcomes for patients with glioblastoma by offering efficacious targeted immunotherapeutic combinations.

This project will identify highly repurposable drugs or drug combinations to facilitate the development of targeted immunotherapies and combination immunotherapies for glioblastoma.

2020 Award 5
All Cancers

Pilot Award
All Cancers

Elucidation of the cancer cell co-translational interactome for development of a new class of therapeutic peptide inhibitors.

Principal Investigator

Our long-term objective is to determine the co-translational interactome of cancer cells for development of a novel class of interference peptides for cancer therapeutics. Intracellular protein-protein interactions (PPI) are critical for most pathophysiological processes, including tumorigenic signaling pathways. For disruption of such pathways, inhibition of PPIs is becoming an important therapeutic modality. However, limitations of this approach have hindered progress: The binding interfaces in PPIs are generally large and can be inaccessible to interfering therapeutics. A potential circumvention to these limitations is based on the recent discovery that many constitutive, PPIs and multi-protein complexes are assembled by co-translational interactions. In this mechanism, a fully-formed protein interacts with the emerging N-terminus of its partner protein during translation. A co-translational interference peptide (CoTiPep) that mimics the interacting region on the nascent peptide will bind the interacting partner and disrupt the interaction. This approach overcomes limitations of previous strategies to disrupt PPIs since the region of co-translational interaction is linear and exposed. Elucidation of cancer-related complexes generated by co-translational interactions delivers a unique opportunity to design peptides to disrupt pathological PPIs. We will take advantage of this opportunity by pursuing two Specific Aims. In Aim 1 we develop a novel technique for global elucidation of co-translational interactions and their binding interfaces. In Aim 2 we develop specific interference peptides that inhibit co-translational interactions of selected colon cancer-related PPIs. Successful completion of these studies will form a robust experimental platform for discovery of novel CoTiPep against colon cancer-related interactions for pre-clinical studies of cancer therapy.

In Other Words

Intracellular complexes are critical for most pathophysiological processes, including tumorigenic signaling pathways. Inhibition of complex formation by interfering with protein-protein interactions (PPI) is becoming an important therapeutic modality. Our long-term objective is to develop a novel class of interference peptides for cancer therapeutics taking advantage of recent evidence that many PPIs exploit nascent, newly synthesized peptides, not mature proteins.

2020 Award 6
Lung Cancer

Pilot Award
Lung Cancer

Determining the mechanism of resistance to 3rd generation EGFR TKIs in lung cancer.

Principal Investigator

Lung cancer is the leading cause of cancer death in the USA with estimated 230,000 new cases and 160,000 deaths this year. Recently, multiple genetic mutations have been identified in patients with lung cancer. These mutations are responsible for the tumor growth and are valuable targets for treatments. In fact, epidermal growth factor receptor (EGFR) is found to be mutated in lung cancer and multiple drugs that target EGFR activity were developed. These drugs are very successful in shrinking tumors and extending life of patients with a tolerable side effect profile. Unfortunately, almost all patients treated with these drugs develop resistance and their cancers progress. Although novel drugs are being developed the exact mechanism that causes resistance is not identified yet. Understanding how this resistance occurs is vital in delaying or preventing resistance, thus prolonging response and survival. In this project, we aim to determine the mechanism of resistance to 3rd generation EGFR inhibitors providing new targets for treatment. Combining EGFR inhibitors with drugs that prevent resistance development could be introduced to early phase clinical trials within few years.

In Other Words

In this project, we aim to understand the underlying mechanism of resistance mutations that develop after targeted therapy. This will lead to designing clinical trials using combination drugs to overcome resistance.

2020 Award 7
Brain Cancer

Pilot Award
Brain Cancer

A first-in-class senolytic to inhibit glioblastoma and treatment resistance.

Principal Investigator

Glioblastoma (GBM) is the most common and the most lethal brain cancer with no curative therapy available. Challenges inherent in developing effective GBM therapeutics include resistance to standard treatments such as radiation and chemotherapy, genetic and molecular heterogeneity, and dynamic adaptability of stem-like GBM cells. Cellular senescence is implicated in tumor initiation, progression, and treatment resistance. Recent studies collectively suggest that senescent GBM cells promote tumor progression and recurrence, by secreting multiple cytokines and growth factors into tumor microenvironment, referred to as senescence-associated secretory phenotype (SASP), and by enhancing cancer stemness via epigenomic reprogramming. Therefore, elimination of senescent tumor cells can be a potential therapeutic approach, especially in combination with standard therapies. Research in this direction, however, has been underexplored. Critical hurdles include 1) the lack of the cell surface markers that can prospectively identify the cells undergoing senescence programs and 2) far more dynamic and heterogeneous nature of senescence than suggested by the traditional view of senescence as an irreversible, static state. 
We have discovered that CD142 is an enrichment marker for senescent GBM cells, through a high-throughput cell surface marker screen coupled with transcriptome analyses. Furthermore, activation of CD142 by its ligand Factor VII reduced SASP activity and induced tumor cell death. We will test that Factor VII-CD142 signaling axis is a novel senolytic pathway that can be developed as a potent therapeutic approach. Our proposal will provide the opportunities to better understand tumor senescence and design effective therapeutic strategies.

In Other Words

This proposal aims to discover a novel and effective therapeutic approach based on senescence-associated cell death signaling in GBM.

2020 Award 8
Blood Cancer

Pilot Award
Blood Cancer

Development of a new therapeutic for peripheral T-cell lymphoma.

Principal Investigator

T-cell lymphomas are heterogeneous and aggressive, and affected patients have unfortunately short, overall rates of survival. Unlike B-cell lymphoma patients that have benefitted considerably from several available treatments such as rituximab and inhibitors of the B-cell receptor pathway, there are alarmingly few available therapeutics that target T cell lymphomas. In pilot studies, we found that CD6 is present on all the patient T cell lymphoma samples examined, and determined that upon binding, our high affinity anti-CD6 monoclonal antibody (mAb) is efficiently internalized by these cancer cells, rendering this mAb an ideal candidate to formulate an antibody-drug conjugates (ADC) to kill the cancerous T cells. Furthermore, we have already humanized this anti-CD6 mAb as part of another project, indicating that this mAb can be translated into the clinic in a timely manner once its therapeutic potential is established. In collaboration with hematopathologists, T cell lymphoma clinical specialists and basic scientists at Cleveland Clinic, in this project we will establish the expression profile of CD6 in different patient T-cell lymphoma samples, and more importantly, we will test the efficacy of our anti-CD6 mAb-based ADC for treating T cell lymphomas using patient-derived xenograft (PDXs) models in NSG mice.  Results from this project should provide a rationale to further develop our anti-CD6 mAb-based ADC as a novel, promising targeted therapy for patients with CD6+ T cell lymphoma.

In Other Words

This project aims to find better therapies for T cell lymphomas by evaluating the treatment efficacy of a CD6-targeted antibody drug conjugate (ADC).

2020 Award 9
Colitis Associated Colorectal Cancer

Pilot Award
Colitis Associated Colorectal Cancer

Role of NCAPD3 in preventing ROS accumulation and the development of Colitis Associated Cancer.

Principal Investigator

In this proposal, we aim to identify new mechanisms that lead to the development of Colitis associated cancer (CAC) and identify possible new ways to prevent CAC development. CAC develops in patients diagnosed with the Inflammatory Bowel Disease, Ulcerative colitis (UC). 1,000,000 people are affected with UC in the U.S., and the incidence is rising, thus resulting in more people who are at risk for developing CAC. UC patients experience chronic intestinal inflammation. Studies have shown that this chronic inflammation leads to chemical reactions, generating oxygen molecules that can harm DNA. Our published studies identified the NCAPD3 protein as a new regulator of these chemical reactions that may act to prevent the generation of harmful oxygen molecules in intestinal cells. Since NCAPD3 levels are decreased in UC patients, and experiments from our lab and others show that decreased NCAPD3 levels cause molecular changes in cells that can initiate tumor development, we hypothesize that decreased NCAPD3 protein levels in UC patient intestinal cells cause accumulation of harmful oxygen molecules which damage DNA and promote tumorigenesis. We will manipulate the levels of NCAPD3 in healthy control, UC, or CAC patient-derived intestinal cells and utilize advanced biochemical and molecular assays, as well as microscopy techniques to measure levels of harmful oxygen molecules, identify their source, and test their downstream effects on DNA. These studies will significantly contribute to our understanding of the molecular events leading to CAC development and could identify specific antioxidants as new therapeutics to prevent CAC development.

In Other Words

This project aims to identify new dysfunctional pathways that lead to the development of colitis associated colorectal cancer by analyzing the mechanisms that result in accumulation of harmful oxygen derivatives and subsequent instability of the genome.

2020 Awards 11
Ovarian Cancer

Pilot Award
Ovarian Cancer

Targeted Immunotherapy of Epithelial Ovarian Carcinoma.

Principal Investigator

Epithelial ovarian carcinoma (EOC) is the most prevalent and lethal form of ovarian cancer in the United States, representing ~80-85% of all ovarian cancers. While the majority of women respond well to initial treatments, most of them experience a recurrence of ovarian cancer and eventually becoming resistant to current drug therapies. The high rate of EOC recurrence and the low five-year survival rate indicate an urgent need for more effective ways to control this disease. We have identified anti-Müllerian hormone receptor type 2 (AMHR2), as a promising and novel target for EOC therapy. Our recent results reveal that a specific antibody response to the extracellular domain of AMHR2 (AMHR2-ED) is the predominant cause of EOC cell death. These findings indicate that targeting AMHR2-ED specific monoclonal antibody will be a preferable and much-needed approach to treat EOC.  We hypothesize that anti-tumor responses against EOC can be effectively achieved by the humanized AMHR2-ED antibody. We will test our hypothesis by testing the potency of therapeutic humanized AMHR2-ED monoclonal antibody against EOC.  We will characterize the AMHR2-ED humanized antibody and will evaluate the efficacy of this humanized antibody for effective inhibition of human EOC, derived from patients. Accomplishing this aim will identify the preferable and effective treatment for EOC, which kills 53% of women within 5 years of diagnosis.  The results of our study targeting the humanized AMHR2-ED antibody will elucidate the potential for an immunologic-based approach for treating EOC. Our proposed strategy represents a unique, paradigm-changing, and much-needed way to regulate EOCs.

In Other Words

The high rate of Epithelial ovarian carcinoma (EOC) recurrence and the low five-year survival rate indicate that there is an urgent need for more effective ways to control EOC. We hypothesize that the extracellular domain of the Anti-Müllerian hormone receptor 2 (AMHR2-ED)-specific antibody may serve as a novel, and effective reagent to control EOC. This proposed study of the humanized AMHR2-ED antibody will elucidate the strong potential for an immunologic-based approach to treat human EOC.

If it Weren't for Funding From VeloSano

square image
square image
square image

“For us, it’s a catalyst,” Justin Lathia, PhD, says about the philanthropic support his lab receives from VeloSano, the year-round community-driven fundraising initiative to support lifesaving cancer research at Cleveland Clinic.

VeloSano’s flagship fundraising event, the annual “Bike to cure” weekend, takes place this year on July 19-21. Since the inaugural ride in 2014, more than $17 million has been raised, with 100% of those funds supporting 115 cancer research projects across 11 different institutes and regional locations. Beyond the $17 million allocated by VeloSano, over $14 million in additional, external grants has been received due to the promise shown by VeloSano-funded projects.

“The unfortunate reality in research is that good ideas are a dime a dozen,” says Dr. Lathia, Vice Chair of the Department of Cardiovascular & Metabolic Sciences at Cleveland Clinic Lerner Research Institute. “The challenge is getting an idea funded and off the ground. For that you need proof of principle, you need preliminary data, you need a demonstration – because there’s nothing worse than not knowing if an idea will work. And that’s where philanthropy comes in.”

Dr. Lathia’s research focuses on glioblastoma, the highly aggressive form of brain cancer that took the lives of U.S. Senators John McCain and Ted Kennedy, and former National Institutes of Health (NIH) Director Bernadine Healy, who was Cleveland Clinic’s first female Chair of the Lerner Research Institute.

Dr. Lathia says to think about research funding like an investor: Would you invest in a company that doesn’t have a product? Would you invest in a company that doesn’t have a prototype? “The answer’s no, right?” he says. “So it’s that initial funding that we need in order to ratchet it up and get additional funding.”

VeloSano’s Pilot Awards Provide Essential Seed Funding

His lab has received three Pilot Awards from VeloSano. The funding from those awards furthered his research and already has helped secure several larger federal grants.

The first Pilot Award, in 2014, supported Dr. Lathia’s investigation into why glioblastoma are immunosuppressive – meaning that the body’s immune system doesn’t work properly to fight the tumor cells. “We have been laser-focused on a group of cells that sit in your bone marrow and only become activated during disease, so these cells are called suppressor cells,” he explains. “It turns out that suppressor cells seem to be really high in glioblastoma patient blood as well as in the tumor micro-environment. We’ve been working on this for a while, and one of the things we figured out is that we can actually kill them by giving low-dose chemo.”

This project led Dr. Lathia’s team to discover that there are differences in male and female glioblastoma. The team believes there are genetic differences in the immune system and differences in reaction overall to glioblastoma – which is a huge discovery, says Dr. Lathia. “This entire project started with me being wrong about a hypothesis and I feel like every time I’m wrong again, it gets more interesting,” he says, laughing. “To me, that’s the exciting, tantalizing part of research – when I’m wrong.”

This research now is in a Phase 1 clinical trial and, thanks to the seed funding from VeloSano, recently was awarded a prestigious, five-year, $2 million grant from the National Institute of Neurological Disorders and Stroke.

His lab received a second Pilot Award in 2016 to help fund another glioblastoma research project. “Over the past seven years my lab has been working to demonstrate that there are specific channels between cells that allow them to communicate with each other. These are really important for the cancer cells to grow and expand,” Dr. Lathia says. Although the research received an NIH R01 grant, the funding did not support the development of a drug therapy. The VeloSano grant provided support to try to develop inhibitors to a specific channel that’s only used by glioblastoma cells. The research continues and has a patent pending on the drug strategy.

The third Pilot Award was given last year and supports the research of cell-to-cell communication in triple negative breast cancer, the most aggressive type of breast cancer. Dr. Lathia’s team discovered that cancer stem cells play a significant role and that a protein once thought to suppress tumors actually may support tumor progression by aiding in cell-to-cell communication. Working collaboratively with Ofer Reizes, PhD, holder of The Laura J. Fogarty Endowed Chair for Uterine Cancer Research and a six-year VeloSano rider, the team is developing new therapies. They’ve already filed for a drug patent and have received promising feedback from a larger scale grant funder to support additional studies.

‘An Amazing Investment’

In addition to benefiting from VeloSano, Dr. Lathia participates, raising a minimum of $1,000 to ride 25 miles and serving as the captain of the Lerner Research Institute team. He says VeloSano weekend gives cancer researchers the rare opportunity to interact with the public about their work.

“At the Friday Night Kickoff Party during VeloSano weekend, I meet a lot of people; when I’m riding, I talk to people,” he says. “I thank them for riding and explain about the work in the lab. VeloSano really gives us the chance to tell the community what we do and what we’re up to in the lab. To me, it’s an amazing investment. And it’s done in a way that every single penny that is raised comes back to cancer research and is spent in a year.”

Dr. Lathia is passionate about his work at Cleveland Clinic. “This is something we do better than any other place I’ve seen,” he says. “We have the ability to move quickly to make an impact on human health.”

 

VeloSano Funding Leads to Major Grant from NIH

square image
square image
square image

A Cleveland Clinic cancer research project, which received initial funding from dollars raised during VeloSano 2 in 2015, has been awarded a $4.7 million grant from the National Heart, Lung and Blood Institute (NHLBI), part of the National Institutes of Health.

The new funding will support a Cleveland Clinic-led research consortium, which will focus on developing strategies to prevent cancer-associated thrombosis (blood clot formation), a potential side effect of cancer treatment.

Seed Funding Pays Off
In 2016, Keith McCrae, MD, Director of Hematology at the Taussig Cancer Institute, and Alok Khorana, MD, Director of the Gastrointestinal Malignancies program at the Taussig Cancer Institute, received a VeloSano Impact Award for $150,000 per year over three years, initiated through Cleveland Clinic's Center of Excellence in Cancer Thrombosis Research. The seed funding allowed the research to advance and become eligible for federal funding.

Dale Shepard, MD, PhD, Director, Taussig Cancer Institute Phase I and Sarcoma Programs, and Co-Medical Director of VeloSano, is please about the grant from NHLBI. "Both Dr. McCrae and Dr. Khorana, who holds the Sondra and Stephen Hardis Chair in Oncology Research, have been working on cancer thrombosis for a long time," he says.

Federal funding for medical research continues to be extremely competitive, and Dr. Shepard says that philanthropic support of the initial stages of research is crucial to  securing additional support. “NIH funding is now often directed toward teams rather than individual labs. VeloSano is helping to fund Cleveland Clinic’s Centers  of Excellence to support our investigators as they develop more comprehensive research programs to work together instead of in silos.”

VeloSano Support Makes a Difference
Dr. Shepard believes that more external funding from projects supported by VeloSano will occur as more of the initial research is completed. "The roughly $12.4 million of external funding received so far is primarily from the first two years of support from VeloSano," he says. "Many of the projects from subsequent years have not yet been completed or those results are in the process of being used to write grant proposals."

Dr. Shepard cautions that it takes more than a great idea to get funding for cancer research. "It takes preliminary research to show that the investigators can do the work, that the work is feasible and that there is a good chance for success," he says. "This is one of the most important ways VeloSano can help push forward the next steps toward better cancer therapies and perhaps a cure: Funding great ideas by our Cleveland Clinic researchers and allowing them the resources to potentially move those ideas closer to reality."

2019 Top Fundraisers

2019 Top Fundraising Riders

  1. Stewart Kohl
    $150,205
  2. Paul Dolan
    $86,570
  3. Leg Pagon
    $33,846
  4. John & Eliza Saada
    $32,600
  5. Matt Litzler
    $26,216
  6. Greg Avis
    $26,100
  7. Anne Avis
    $25,000
  8. Craig Manchen
    $23,500
  9. Bill Mulligan
    $21,719
  10. Mat Gleeson
    $21,152

2019 Top Virtual FUNDRAISERs

  1. Bob Rich
    $42,070
  2. Frank Porter
    $13,500
  3. Sally Wajahn
    $11,555
  4. Jorge Garcia
    $9,195
  5. Alan Lichtin
    $5,500
  6. Michael Cucciarre
    $4,365
  7. Nicole Peters
    $4,290
  8. Charis Eng
    $4,137
  9. Jame Abraham
    $4,120
  10. Zumi Pig
    $3,710

2019 Teams                                                                       

Team Name Riders & Virtual Fundraisers Total Dollars Raised
Cleveland Clinic: Taussig Cyclotrons 296 $423,520.01
Cleveland Indians 97 $239,231.50
The Riverside Company 49 $211,587.61
Cleveland Clinic: Make it Rain 155 $155,997.05
The Big Galoots 79 $148,635.79
Team Oatey 109 $120,110.52
Cleveland Clinic: Wheels of Steel - Buildings & Properties 41 $97,388.46
Jones Day 33 $94,660.31
Sandy's Domestiques 21 $93,940.00
Case Comprehensive Cancer Center 90 $93,824.28
Team Metro Lexus Elite 49 $87,125.57
Team PwC 58 $85,477.19
Cleveland Clinic: CC Ventures-Investment-Innovations 36 $74,970.39
Cleveland Clinic Children's 89 $71,328.61
Cleveland Clinic: Nursing Institute 73 $71,271.50
Spin for Stu 41 $70,515.44
The Lerner Foundation 29 $69,836.00
Team Key 69 $68,269.63
VeloSano United 40 $65,971.00
Team KPMG 35 $57,810.37
Hudson Velo 28 $54,484.61
Vocon 23 $53,807.31
Team 1:9 43 $53,370.01
LitzlerAutomation 16 $51,314.86
Cleveland Clinic: Lerner Research Institute 53 $47,729.01
Donley's 15 $45,728.00
Team Oswald 26 $42,174.19
Team BDO USA 11 $39,770.00
Sherwin-Williams 16 $38,572.00
Team Wendy 12 $37,760.00
ADCOM CYCLING TEAM 36 $37,673.00
Wheeling for Healing 10 $37,490.00
CBRE 16 $31,995.00
Calfee2019 15 $29,085.00
Team RSM 30 $28,650.00
Glenmede Team 13 $27,668.75
BrandMuscle 30 $24,778.68
Team Trishy Strong 34 $24,238.00
Cleveland Clinic: Team RT-PLMI 26 $24,115.90
StARTinCLE 3 $23,482.00
Cleveland Clinic: Region Legion 22 $23,259.90
Squire Patton Boggs (US) LLP 19 $23,045.00
Cleveland Clinic: Sleep Cycles 14 $21,987.30
GLC Cheesy Riders 18 $20,950.00
WKYC 18 $20,672.34
Goodyear 11 $20,227.56
Velo Vino 17 $20,174.50
Team M.A.G. 21 $18,260.00
Team Accenture 17 $17,866.45
Team Hileman 21 $16,416.00
Cleveland Clinic: A Team 11 $15,636.00
Sam LiBassi Foundation 12 $15,011.00
Flying Frank 6 $14,600.70
Cleveland Clinic: Team International and Protective Services 28 $14,106.00
Team Marcus Thomas 9 $13,798.00
Cleveland Clinic: Community Care 17 $13,478.00
Team GARDINER 5 $12,745.00
Cleveland Clinic ITD 9 $12,720.00
Cleveland Clinic: Fairview Hospital 13 $12,437.00
Cleveland Clinic: CyclOps 12 $11,721.00
#Teamallynmona 8 $11,071.00
American Greetings 8 $10,597.71
Ancora 5 $10,136.00
Team FOX Sports 3 $9,707.50
Assurant 7 $9,568.37
Team Classic Lexus 7 $9,500.00
Cardinal Health 4 $9,361.10
we are cARe-IAN's 4 $9,194.00
Nestle VeloSano 6 $9,078.00
Tony's Crew 8 $8,501.00
Team Fifth Third 7 $8,025.00
Cleveland Clinic Avon ED lifesavERs 9 $8,001.00
Michelob Ultra 4 $7,956.00
Cleveland Clinic: Team South Pointe 23 $7,564.00
Plante Moran 5 $7,490.27
Papa's Peddlers 3 $7,326.00
KJK (Kohrman Jackson & Krantz LLP) 8 $7,233.00
Grant Thornton 8 $7,097.00
Team Lilly 7 $6,955.00
Say Bye-ke to Cancer! 5 $6,652.20
Cleveland Clinic: Pepsin Pedalers 8 $6,410.00
Colliers International 2 $6,410.00
Team Deloitte 6 $6,400.01
Team McDonald Hopkins 11 $6,362.00
Luciano Family Foundation 2 $6,291.01
Trane CLE 8 $6,125.00
Team Ulmer 6 $5,872.00
Eddie's Angels 9 $5,830.00
Fidelity Roadfrogs 5 $5,700.00
Team Esteem 8 $5,625.00
Team Chick-fil-A 4 $5,510.45
Team Brawner 3 $5,420.00
North Coast United 6 $5,198.99
Brookfield Properties 3 $5,150.00
Akron Children's Hospital 4 $5,060.00
MERRILL LYNCH/BANK OF AMERICA 2 $5,043.69
Evergreen Cooperatives 9 $5,000.00
CBIZ 3 $4,810.00
Beans and Weanies 4 $4,733.00
Hitachi Healthcare Americas 5 $4,695.00
Snavely Group 5 $4,365.00
Team EY 2 $4,345.00
Smucker's 4 $4,288.84
Cleveland Clinic: Psycle: Pediatric Behavioral Health CC Children's 3 $4,220.00
Team Northern Trust 1 $4,050.00
Start to Finish Fitness 2 $4,000.00
Cleveland Clinic: Brainiacs 5 $3,892.50
Fit Technologies 4 $3,855.00
Siladi 2 $3,812.75
The Wheel Deal 3 $3,685.82
Fangin' it on Pushies 3 $3,500.00
Quicken Loans 3 $3,376.00
Cleveland Clinic: Quality & Patient Safety 4 $3,375.00
Frantz Ward LLP 3 $3,333.00
DOMINATORS 1 $3,170.74
Team Brace 3 $3,145.00
Clot Busters/ Red Vascular Flow/ Dynamic Perfusion/ Reperfusion Quintet 3 $3,120.00
Two Tired 4 $3,060.42
Cleveland Clinic Patient Experience 3 $2,970.00
Cleveland Clinic: Akron General 3 $2,970.00
Chagrin River Capital 4 $2,840.00
We Are Family 2 $2,760.00
Team Cinghiale 3 $2,735.00
Donut Lettuce Stop Rollin' 2 $2,700.00
Murray Pranksters 3 $2,630.00
Peddlin' for Patty! 2 $2,610.00
Neundorfer Family 2 $2,550.00
Team A 2 $2,496.00
Kick Some Carcinoid 2 $2,300.00
J Team 2 $2,293.00
Team ZOOMba 3 $2,278.00
Team Veni Vidi Vici 2 $2,170.00
Team Apple 2 $2,165.00
2BikeCrew 2 $2,116.00
Cleveland Clinic: iCyCLE 4 $2,030.13
Vox Mobile 4 $2,010.00
Mueller Design 2 $2,000.00
Welch's Wheelers 2 $2,000.00
Cleveland Clinic London 12 $1,910.00
the Scott Tribe 2 $1,871.00
Flo's Riders 2 $1,835.00
TnT Hope Riders 2 $1,765.00
Pedal to the Metalers 3 $1,752.54
MegaCycle 2 $1,600.00
Bayer 1 $1,595.00
Cleveland Clinic Dermatology 3 $1,590.14
Thirsty Dog Brewing Co. 2 $1,550.00
Faster Than A Speeding Turtle 2 $1,535.00
IntegraConnect 1 $1,520.00
25 Since Stage 4 1 $1,500.00
Ed & Sandy 2 $1,500.00
Campus International School 3 $1,255.00
Dad and Daughter 2 $1,200.00
Team Breast Friends 6 $1,195.00
Company Car 1 $1,150.00
nora by Interface 2 $1,114.99
Colonial Auto 2 $1,100.00
U.S.NavyVets 2 $1,060.00
DiFranco Duo 2 $820.00
Hiccup 2 $750.00
The Blue Crew 2 $750.00
The Honey Badgers 2 $635.00
Cottonwood Cancer Crushers 5 $570.00
LAV 1 $500.00
CC Employee Wellness 2 $105.00
imagers 1 $35.00
Cleveland Clinic: Hillcrest Lifesavers 1 $25.00
 

Living Hope

Our Living Hope community of Riders, Virtual Fundraisers and Volunteers who are current cancer patients, people in recovery and those who are cancer survivors bring to VeloSano stories of their journeys and their own personal reasons for “Why I Ride”.

Living Hope

This special community provides Hope for recovery; Hope for a cure; and Hope for the day when there will be no cancer. Every year we unite to share in their journeys and to celebrate recovery, remission and support those who are battling cancer. Every year we Bike to cure.

We honor our Living Hope community — you inspire us!

living-hope-162px.png

Our Partners

The ability to provide 100% of participant raised dollars to cancer research would not be possible without our Partners.

VeloSano's flagship fundraising initiative, "Bike to cure" weekend, attracts participants from all over the world. One-day ride options range from 12-100 miles and a Two-Day 190+ mile experience is also available. Each rider commits to raise a particular amount of money and 100% of the dollars raised are awarded directly to research by spring of the following year. Corporate and Foundation Partnerships offset VeloSano "Bike to cure" operational expenses through monetary or in-kind services to ensure that not one dollar raised is spent on anything other than research.

Please scroll through the list below to view all of our amazing partners:

Founding Partners

Cleveland Indians
Kohl

Supporting Partners

Adcom Group
Jones Day
Lexus
Zack Bruell Events

Contributing

Celgene
cleveland.com
DiGeronimo Companies
KeyBank
Lilly Oncology
Michelob ULTRA

Spoke

Amgen
ASSOS
Hileman Group
Hilton Cleveland
The Lerner Foundation
Oatey
Panera Bread
RSM
Smucker's
Van Cleef & Arpels

Pedal

Accenture
Barbasol - Pure Silk
Donley's
Turner
The Stielau Foundation

Axle

Assurant
Brandmuscle
CBRE
Coca-Cola
Genentech
Giant Eagle
GOJO
Gross Residential
MCPc Family Charities
Rich's

Media

Cleveland's Star 102
ESPN Cleveland
Fox Sports Ohio
Spectrum
iHeart Radio
WKYC

Special Thanks

Bike Cleveland
City of Cleveland Ohio
Cleveland Clinic Emergency Services Institue
Cleveland Clinic Sports Health
City of Cleveland Water
Hirobel
Petitti Garden Centers
South East Golf Car Company
 
A
Abelson, Tom
Abraham, Jame
Adams, Richard
Adelstein, David
Ahluwalia, Manmeet
Aldridge, Geoff
Allen, Kyle
Al-Nimer, Sara
Amato, Michelle
Anderson, David
Arian, Keith
Arian, Leslye
Arth, Samantha
Avis, Anne
Avis, Greg
Avis, Sandra
Avis, Todd
B
Bachoo, Savitre
Bailey, Susie
Baker, Mark
Balch, Sarah
Balla, Mike
Baratian, Marcus
Barnhouse, Joanne
Barnhouse, Tori
Bauer, Emily
Baumgard, Michele
Beal, Emily
Beauchamp, Brian
Behm, Pat
Bell, Chip
Bell, Joy
Bender, Allen
Benjamin, Robert
Berg, Kelly
Bernot, Barrett
Bernot, Jessica
Bizjak, Ellen
Bolwell, Brian
Booth, Steve
Borish, David
Bosner, Brittany
Box, Gregory
Brady Curtis, Erin
Brand, Beth
Brandt, Mark
Brawner, Jen
Brewster, David
Brown, Mark
Budd, George
Budenz, Jaclyn
Burger, Todd
Burnham, Pat
Burnham, Ross
Burns, Aeron
Butze, Kenneth
Bycina, Dina
Byrnes, Marcus
C
Caban, Angel
Caban, David
Callsen, Julie
Camerato, Gina
Capizzani, Tony
Carney, Allison
Carraway, Hetty
Case, Rob
Casey, Matt
Cave, Taylor
Chamberlin, Janelle
Chase, Mike
Chylla, Loren
Ciarimboli, Gino
Cicarella, Tom
Cicero, Colleen
Cobb, Kendalle
Coburn, Heidi
Coburn, Michael
Cohen, Joanne
Cohen, Nan
Comiskey, Kelly
Connor, Sean
Constantine, Tony
Converse, Chandler
Cronauer, Joseph
Cseplo, Paul
Cucciarre, Michael
Cusato, Paul
Custer, Kevin
D
Daher, Gerard
Daley, Tiffany
Dandes, Jonathan
David, Judy
Deal, Chad
Deal, Logan
Dean, Robert
Desai, Amar
Desantis, Phyllis
Deuschle, James
Diaz, Marcela
Dieleman, Darren
DiLillo, Rocco
DiLillo, Ruthann
Dlouhy, Patricia
Dolan, Paul
Donley, Debbie
Donley, Mac
Doren, Dave
Dowdall, Coleen
Dreier, Don
Duffy, Meg
Duncan, Daniel
Dyer, Jolene
E
Easa (Swartzlander), Sheila
Easton, Chris
Easton, Patricia
Edelman, Kenny
Ehrbar, Jeff
Elios, James
Ellman, Kevin
Eng, Charis
Eshleman, Kate
Estfan, Bassam
Estfan, Yasmeen
F
Faturos, David
Fazioli, Don
Ferguson, Rachael
Ferranti, Richard
Finley, Logan
Firrell, Claire
Fisher, Dean
Fisher, Ryan
Fleming, Kristen
Forbes, Judy Ann
Foster, Christopher
Frazier, Rebecca
Freeman, Thomas
Furlong, Ben
Furlong, Beth
Furlong, Bryan
Furlong, Meghan
G
Gagnon, Mark
Gamier, Pamela
Garcia, Jorge
Gard, Phil
Garson, David
Gavigan, Michael
Geiger, Matthew
George, Mariah
Gerson, Stanton
Gingrich, Stephanie
Gisel, William
Gleeson, Mathew
Gleydura, Michael
Gorman, Christopher
Grinnell, Dave
Grisko, Jerry
Guzowski, Lindsay
H
Haberny, Logan
Hale, James
Halloran, Susan
Hamilton, Aaron
Hamilton, Betty
Hamilton, Miles
Hamilton, Randy
Hancock, Kelly
Harries, Anna
Hart, Kathy
Haugli, Dana
Haverfield, Gage
Hearns, Brendan
Hearns, Graham
Hearns, Kelsey
Hearns, Kerianne
Hein, Christina
Henderson, Mark
Henderson, Meghan
Henkel, David
Henkel, Peter
Hill, Amy
Hiznay, Aleksandra
Hodgeman, Brittany
Homans, Lesley
Hoy, Kevin
Hurtuk, Brian
Huxtable, Rob
I
Isaacson, Bud
Isaacson, Kathy


 
J
Jackson, Judy
Jacobs, Jeremy
Jacobs, Michael
Jacobs, Morgan
Jewell, John
Jewell, Rachel
Johngrass, Rick
K
Kalafatis, Lara
Kalaycio, Matt
Kaouk, Jihad
Karklin, Steve
Kelly, Mar-Qilia
Kennedy, Curran
Kiener, Mary
Kiener, Steve
Kieser, Tara
Kingston, John
Klein, Frank
Klein, Larry
Koc, Omer
Kohl, Stewart
Kohn, Steven
Kolesky, Lindsey
Krankowski, David
Krejci, Lisa
Krishnamurthi, Smitha
Kuebler, Scott
Kula, Allison
Kula, Casey
Kula, Jeff
Kula, Lisa
L
Larson, Jenna
Lathia, Justin
Lavalley, Kylie
Lee, Richard
Lehman, Dennis
Lehtinen, Katherine
Leonard, William
Leonard, Brian
LiBassi, Elizabeth
Lichtin, Alan
Lindemann, Connie
Linehan, Matthew J
Litzler, Matt
LoCascio, Larry
Logan, Eric
Lopez, Gregory
Luciano, Daniel
Lupkin, Kim
Lupkin, Urmas
Lynch, John
Lynn, Kevin
M
Madonia, MaryBeth
Madonia, Russell
Magden, Shelley
Maggiotto, Amanda
Majhail, Navneet
Malik, Christopher
Malone, Mary Kay
Manchen, Craig
Mann, Herrick
Manning, Joe
Mannor, Keith
Manos, Steven
Manosky, Matt
Mapp, Peter
Marazita, David
Marous, Jim
Marx, Edward
Mayor, Tom
McCrae, Keith
McCullough, John
Mcdonnell, Matthew
Mcintyre, Kevin
McKinley, Stacey
McManamon, TJ
Madonia, Russell
Mendelsohn, Amanda
Mian, Omar
Mihaljevic, Maya
Mihaljevic, Nella
Mihaljevic, Tomislav
Mikhail, Bishoy
Miller, Mick
Mimura, Laura
Mocilnikar, Jessica
Mocilnikar, Robbie
Mog, Erin
Monga, Manoj
Monteleone, Emily
Montgomery, Jeff
Mooney, Sarah
Moore, Ed
Morabito, Jennifer
Muckley, Ed
Mulligan, William
Muniak, Katie
Murfey, Latham
Murphy, Erin
Muyskens, Neil
Myers, Robert
Mylen, James
N
Neale, Kyle
Neff, Anne
Negret, Camila
Neundorfer, David
Neundorfer, Jennifer
Nichols, Tim
Niezgoda, Julie
 

O
Oatey, Gary
Oatey, William
Olbrysh, Bob
Olson, Scott
Omori, Sue
Onders, Michael
Ornstein, Moshe
P
Pagon, Len
Palliser, Brian
Palliser, William
Pappas, Amy
Pate, Mary Beth
Patel, Bhumika
Patel, Jill
Payne, Carolyn
Payne, Laura
Pecoraro, Cory
Pennell, Bob
Perry, Louis
Peters, Matthew
Peters, Nicole
Petitt, Lori
Phillips, Scott
Pho, Danny
Pig, Zumi
Polakoff, Sacha
Pollock, Julia
Pollock, Larry
Porter, Frank
Poulter, Kim
Poulter, Scott
Prueter, Katie
R
Ramsay, Evangeline
Reagor, Craig
Reichart, Sharon
Reichenbach, John
Reizes, Ofer
Restivo, Neal
Rhone, Allyson
Rhone, Jennifer
Ricci, Kristin
Rich, Bob
Rich, Howard
Rich, Mindy
Rich, Paul
Richards, Tim
Riley, Addison
Riley, Tim
Ring, Ron
Riter, Bill
Roberts, Lynda
Roman, Dana
Rooks, Chuck
Rooks, Jeffrey
Rooks, Morgan
Rosenbaum, Joanie
Ross, Mark
Roth, Allen
Roth, Bryan
Roth, Jaclyn
Roth, Sharon
Roth, Sydney
Rotroff, Daniel
Ruggaard, Randy
Rutherford, Nathan
Ryan, Stewart
S
Saada, Eliza
Saada, John
Sakony, Donna
Samaras, Christy
Samstag, Chris
Sauric, Richard
Schaefer, Michael
Scharf, Leanne
Scharf, Thomas
Scheid, Peter
Schmitt, Karl
Schmotzer, Richard
Schreiber, Kandis
Schreiber, Ryan
Schuster, Janet
Schwarz, Abram
Schwarz, Sarah
Scott, Jacob
Segal, Matt
Shapiro, Marc
Sheetz, Craig
Sheng, Iris
Shepard, Dale
Siladi, Paul
Simoniello, Michael
Singley, Renee
Slemc, Alex
Slover, Sid
Smeller, Michele
Sobecks, Ronald
Sowerby, David
Stachowski, Dana
Stapleton, David
Stapleton, Lisa
Starck, Rebecca
Stevenson, James
Stewart, Doreen
Stoller, Jacob
Stovsky, Katherine
Stovsky, Richard
Strein, Stefan
Strominger, Hannah
Suh, John
Sustar, Jill Olbrysh
Swain, Bart
Swanson, Ray
Swinehart, Diana
 

T
Tagliaferri, Angela
Thomas, John
Thomas, Kevin
Timura, Owen
Timura, Wren
Tischler, Eric
Tischler, Matthew
Titas, Lea
Tomlinson, Benjamin
Travis, Mike
Troianos, Chris
Trudeau, Stephanie
Turek, Frank
Twells, Rodney
Twist, Robert
 

V
Valent, Jason
Valore, Austin
Valore, Bonnie
Valore, Keith
Vassil, Andrew
Vaughn, Kierston
Vince, Geoff
Viny, Steven
Visconsi, Dominic
Visconsi, Julie
W
Waddell, Brenda
Waitkus, Bob
Waitrovich, Kayla
Wajahn, Sally
Waldman, Robert
Walker, Jim
Walker, Margo
Wamelink, Jim
Warsaw, Jerald
Watson, Kate
Weiss, Dana
Weixel, Jennifer
Wheat, Andy
Wheeler, Morris
Wienczkowski, Erin
Winter, Allison
Wittenmyer, Nelson
Wollmann, Amy
Wood, Blair
Wright, Ashley
Wright, Mary
Y
Yee, Pauline
Yu, Jennifer

Z
Zamiska, Lily
Zamiska, Marta
Zelwin, Adam
Zwinggi, Nick
 

Big Wheelers


big-wheelers-no-sponsor.png
Our VeloSano Big Wheelers are Riders who at least double their minimum fundraising commitment or Virtual Fundraisers who raise $1,000 or more. We have more and more Big Wheelers every year and are truly grateful to them for going above and beyond as they fundraise for cancer research at Cleveland Clinic. During VeloSano 6 (2019), we had a total of 460 Big Wheelers that included 402 Riders and 58 Virtual Fundraisers. Each year we treat our Big Wheelers with some special garb, so if you see them sporting their gear around town, be sure to give them a big thank you - they're a big deal!

The Team



 

Founder

Stewart Kohl The Riverside Company

2019 CO-ChairS

Paul Dolan Cleveland Indians
John Saada Jones Day

2019 Medical Chair

Brian J. Bolwell, M.D.

2019 MEDICAL Co-Chairs

Dale Shepard, M.D., Ph.D Medical Co-Chair
Rabi Hanna, M.D. Pediatric Co-Chair

Team VeloSano (pictured above left to right)

Beth Brand, Director
Nicole Peters, Executive Director
Mohammed Farunia, Assistant Director
Kandis Schreiber, Director

2019 Steering Committee

Greg Avis Bangtail Partners
Mark Brandt Pease & Associates
Aeron Burns Lilly Oncology
Kara Carter JumpStart, Inc.
Loren Chylla Adcom
Michael Coburn Nestle USA
Joanne Cohen Cleveland Clinic
Chandler Converse CBRE
Deborah Donley Vocon
Dave Doren Cleveland Clinic
Peter Dougherty Merrill Lynch
Don Dreier Donley’s
Caroline El Sanadi Diamsome Pharmaceuticals
Nathan Green ESPN Cleveland
Tom Hileman Hileman Group
Andy Jones MCPc
Joshua Klarfeld Ulmer & Berne LLP
Denise Kramer Zack Bruell Events
Jeff Kula Cleveland Clinic
Jim LaRose House of LaRose
William Leonard Oswald Companies
Matt Litzler C.A. Litzler Co.
Craig Manchen Highland Group Industries
Peter Mapp Lexus
Valarie McCall City of Cleveland
William Mulligan Primus Capital
Jennifer Neundorfer flashstarts
Len Pagon Next Sparc LLC
Larry Pollock Lucky Stars Partners LLC
Neal Restivo Oatey Co.
Mark Ross PwC
Renee Singley The Lerner Foundation
Mitch Thompson Squire Patton Boggs
Rodney Twells Compass Group of Wells Fargo Advisors
Jacob VanSickle Bike Cleveland
Steve Viny Envision Waste Services LLC
Jerald Warsaw SureSite
Morris Wheeler Drummond Road Capital

Thank you for being part of the VeloSano family.

Your support helps advance innovative cancer research at Cleveland Clinic, making a positive impact on the lives of patients and their families. Thank you!