Daniel Arango, Ph.D.

Funded by the Stuart Scott Memorial Cancer Research Fund

Liver cancer is a leading cause of cancer-related deaths. Its incidence continues to increase, posing a significant threat to public health. A leading risk factor is the chronic exposure to liver stress, which, in turn, enhances the uncontrolled division of cancer cells and tumor growth. Proteins are the functional units within cells. They are made from the instructions stored in DNA and carried by messenger RNA (mRNA) through a process known as translation. Notably, the information stored in DNA is not static and can be modified to alter the outcome of translation to promote cancer growth. Two of these modifications are called ‘RNA oxidation’ and ‘RNA acetylation’, which are induced in liver cells in response to cellular stress, and their levels correlate with tumor growth. Thus, this study will investigate how the interplay between RNA modifications and translation promotes liver cancer. The results obtained in this study will allow for future clinical efforts to fight liver cancer.

Colby Thaxton, MD, PhD

The cells in the human body are constantly subjected to stress, which is linked to changes in cellular metabolism. Our research team, and others, have made connections between these cell conditions and cancer. Our central question is: Can we make a simple blood test that provides an accurate measure of ongoing cell stress and metabolic changes to gauge an individual’s risk of cancer? This test may provide more than just a snapshot measure of cancer risk. For example, the test could be used to measure how lifestyle changes modify cancer risk across the lifespan. To answer our question, we developed expertise that enables rapid measurement of signals in certain blood cells attributed to changes in cell stress and metabolism. Our study will determine if these signals can be used to quantify cancer risk. We will obtain blood samples from individuals without cancer, from individuals who have a condition known to increase their risk of cancer, and from individuals diagnosed with cancer. We will isolate certain cells from these samples and then measure the candidate signals in the cells. We anticipate our studies to reveal that the signals we are measuring will be the lowest in healthy individuals, will increase in individuals with the precancer condition, and will be highest in people diagnosed with cancer. These findings would powerfully validate our technology and suggest that individuals may benefit from our test for the early detection, and even prevention, of cancer.

Evgeny Izumchenko, M.Sc., Ph.D.

Oral cavity squamous cell carcinoma (OCSCC) is the most common head and neck cancers worldwide. Finding OCSCC early, when it’s small and hasn’t spread, allows for more successful treatment, and increases patients’ survival. Unfortunately, most of the patients present at advanced stage when diagnosed. Current method for OCSCC diagnosis (which includes cutting of tissue for laboratory testing), is invasive, costly, and depends on examiner experience, underscoring the need for developing noninvasive cancer detection methods. As OCSCC grows, it accumulates mutations in genes known to play role in cancer progression. Our group and others have reported that such mutations can be detected in saliva of patients with OCSCC. However, no saliva-based screening method for early detection of cancer are currently available. Recently we have developed a method based on the targeted sequencing technology specifically designed to detect OCSCC-associated mutations in saliva and validated this assay using specimens collected in India (a country with a high incidence of OCSCC). While these findings provide the foundation for using this ultra-sensitive and cost-efficient assay in clinical settings, frequency of cancer-driving mutations may vary in patients from different ethnical backgrounds. Our proposal will leverage the unique geographic location of the University of Chicago to evaluate the performance of this test across demographically heterogeneous patient populations, as well as across diverse therapeutic approaches for treatment of OCSCC. A well-validated, saliva-based cancer detection assay with optimal analytical performance would represent a significant clinical advancement in cancer care by reducing mortality, while lowering the socio-economic burden of OCSCC.

Jaehyuk Choi, MD, PhD

Merkel cell carcinoma (MCCs) is a cancer that requires additional research. It is the most deadly skin cancer. Moreover, its incidence is rising, doubling from 2000 to 2013. Until recently, there have been no effective therapies for this disease. Immunotherapies have revolutionized the treatment of MCCs. Roughly 50% of patients respond to these treatments, called PD1 inhibitors. While this is an important advance, there are critical barriers to cure. There are no biomarkers to predict who will respond to treatment. Moreover, there are no treatments for patients who fail immunotherapy. To address this critical unmet need, we have assembled a large clinical cohort of patients with MCCs across multiple institutions. We will subject them to a number of assays designed to identify what immune cells are in each sample and what they are doing. Our goal is to identify patterns that predict who responds to therapy and why or why not. The biomarkers we discover can be immediately deployed to ensure that PD1 inhibitors are only given to patients likely to respond to them. For the rest, our studies will seek to identify novel immunotherapy drug targets. If successful, we can develop new drugs that can be used against these novel targets and test them in future clinical trials. This knowledge will be critical to improve patient care and a key advance to developing a cure for this deadly disease. 

Yuxuan Miao, PhD

Abeloff V Scholar * (Tie for Top Rank)

The treatments for head and neck cancers have been revolutionized by the development of immunotherapies. However, many treated cancer patients often experience relapse. Without a clear understanding of why and how cancer cells resists and relapses after current immunotherapy treatment, it is impossible to design a better immunotherapy, and the current treatments for cancer patients eventually fail due to relapse. For advancing clinical outcomes of future treatments, the goal of this proposal is to identify key mechanisms driving cancer relapse from immunotherapy. Recently, we discovered a special group of tumor cells that resemble the stem cells responsible for regenerating normal tissues. Importantly, these tumor cells appear to be the major survivor of immunotherapy treatment and the cause of tumor relapse. This key finding raised the possibility of targeting the critical molecular programs driving the unique immune resistance of these special cancer cells to prevent cancer relapse. In this study we will develop a new immune-oncology platform for head and neck cancer, so we can achieve rapid genetic manipulation of cancer cells directly in live mice. With this powerful approach we aim to identify the stem cells-specific factors that govern both intrinsic and extrinsic immune resistance mechanisms in head and neck cancer. The information derived from this study will pave the way to the development of the next generation of immunotherapy for head and neck cancers with the capacity to overcome relapse. 

Akash Patnaik, MD, PhD, MMSc

Immune-based medicines are effective in treating and curing subsets of patients across multiple cancers. However, approximately 80% of patients across all cancers fail to respond to immune-based medicines. This lack of clinical benefit is particularly prevalent in aggressive forms of metastatic prostate cancer (MPC) that are resistant to hormonal therapies, where few objective responses to immune-based medicines have been observed.  

The immune system is comprised of cells that can both promote and suppress the growth of the cancer. Our research has revealed that the microenvironment within MPC exhibits scarcity of immune cells. Furthermore, the sparse immune cells that reside within the microenvironment of MPC promote tumor growth and progression. Therefore, there is an urgent need to develop medicines that reprogram the tumor-promoting “bad” immune cells to create a more favorable environment, so the “good” immune cells can enter the tumor and kill cancer cells. The goal of our research is to identify and develop new medicines that can achieve this “switch” in the immune system, to enhance recognition and elimination of the most aggressive forms of prostate cancer. We will test these potential medicines in both mouse models of PC in the laboratory, and in patients with the most aggressive forms of MPC enrolled in clinical trials. Collectively, the findings stemming from this proposal will lead to a deeper understanding of the immune escape mechanisms that allow MPC to spread, and advance the clinical development of novel medicines to reinvigorate the body’s immune system to eradicate MPC.  

Justin P. Kline, MD

Funded in partnership with the Cancer Research Institute through the V Foundation’s Virginia Vine event and Wine Celebration Fund-A-Need

Diffuse large B cell lymphoma (DLBCL), the most common non-Hodgkin lymphoma in the U.S., is often curable with initial treatment. However, outcomes of the ~40% of patients who experience disease recurrence are dismal. Although stem cell transplantation and CAR T cell therapy salvage a subset of patients, most are not candidates for these aggressive treatments or will relapse after receiving them. Thus, relapsed DLBCL remains a critical area of unmet need. Recently, an immunotherapy that stimulates cancer cell engulfment by macrophages through blocking a “don’t eat me” protein called CD47 has shown promising activity in relapsed DLBCL patients when administered with the anti-CD20 antibody, rituximab. However, only 30-40% of patients achieve lymphoma regression after receiving this treatment. My laboratory has devised innovative approaches to enhance CD47 blockade therapy efficacy in relapsed DLBCL. First, by inhibiting a key signaling pathway in macrophages, we can enhance their “appetite” for DLBCL cells in the context of CD47 blockade in vitro. Second, we have developed tools necessary to execute an unbiased genetic screen to identify new and targetable “don’t eat me” proteins on DLBCL cells that enable their escape from macrophage phagocytosis. The major goals of this application are to: 1) enhance the in vivo efficacy of CD47 blockade therapy in DLBCL by disrupting a key macrophage signaling pathway, and 2) identify new “don’t eat me” proteins on lymphoma cells that can be targeted alone and in combination with CD47 blockade therapy. While DLBCL is our focus, many cancers employ mechanisms to evade engulfment. Thus, our results are expected to have broad cancer relevance. 

Nita Lee, MD, MPH

Funded in collaboration with ESPN

EMPOWERED U is a community research program to better understand and address the gaps in cancer research in our diverse communities. Black or African American (AA) patients have lower rates of joining cancer prevention or treatment clinical trials.  For many cancers, Black or AA patients are still diagnosed later or may not live as long as white patients. Many factors such as insurance, poverty, age, other diseases, racism and bias in treatment, and trust of medical research due to prior racism may cause these differences.  As science for cancer treatment advances, the gap will increase if not everyone has equal access to new technology. Patients may miss the chance to join new trials and researchers may miss the chance to better understand disease and treatments in diverse groups.  

This program partners directly with community members to study opinions from patients, caregivers, local community leaders, and medical providers to better understand barriers, myths, fears as well as factors that can improve trials participation and the patient experience.  

The patient and community voice will be captured in focus groups and interviews. The community research team will use this important input to design a Community Clinical Trials Toolkit (booklets, print cards and videos) to better answer questions and worries and support patients to learn about clinical trials. Importantly, we will also create community led education for providers and clinical research teams about community and patient perspectives and best practices to support patients.

Marcia Tan, PhD


Tobacco use, specifically cigarette smoking, is a primary reason that adults develop and die from lung cancer. Adults with low income smoke cigarettes at higher rates than the general population, but they are less likely to go to the doctor and receive help with quitting. It is important to design programs that reach this population outside of a hospital or clinic setting. 

Community health workers (CHWs) are frontline public health workers who work with these communities to help improve their health and connect them to medical services. CHWs are often the first, and sometimes the only, healthcare provider for these adults. Training CHWs on conducting brief interventions for tobacco cessation, or quitting smoking, is important. However, current trainings for tobacco cessation are not always accessible to CHWs because of cost and time-constraints, and because the trainings are not relevant to CHWs’ patients’ experiences. This study will address these issues by adapting a tobacco cessation training specifically for CHWs. We will use information that CHWs have provided about their practices caring for their patients to make the training relevant to their patients’ experiences. We will then give the training to CHWs and test whether the training increased CHWs’ knowledge about tobacco cessation, and whether the training is appropriate for CHWs and their patients. Having more CHWs trained in tobacco cessation will increase the number of adults who receive help to quit smoking, which will help to reduce tobacco use and, ultimately cancer, among adults with low income. 

Ji Yeon Kim, Ph.D.

Funded by the Constellation Gold Network Distributors

Cancer is a disease of uncontrolled cell growth. As the disease advances, the cancer can leave the original site and spread to other parts of the body. The ability to grow and invade is energetically costly though. Thus, cancer cells will modify their metabolism to meet these high energy requirements. This includes aggressively using nutrients to produce more energy (ATP), making building blocks for growth (protein, plasma membranes, DNA) and finding ways to overcome metabolic stress (e.g., reactive oxygen species). In other words, if we can identify metabolic changes that occur only in cancer, then impacting the altered metabolic pathways could enable us to selectively kill cancer cells and not impact normal cells.

We are interested in the metabolism of the sugar molecules fructose and mannose. Cells generate mannose-related metabolites from fructose. We discovered that the balance between fructose and mannose is important when lung cancer becomes aggressive. Only these aggressive lung cancer cells were killed when the conversion of fructose to mannose was disrupted. This project will examine how fructose-mannose metabolism is changed when lung cancer becomes aggressive. We will also determine why this metabolic pathway is critical to keep these cancer cells alive. To accomplish the task, we will remove a critical enzyme in fructose -mannose metabolism, and then utilize a series of experiments to characterize the metabolism of these cancer cells. If successful, this study will provide clues as to why drinking soda (fructose) can increase cancer risk while consuming mannose slows tumor growth. Ultimately, we want to answer whether targeting this sugar pathway can help treat patients.

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