Five University of Florida Health Cancer Center members have been awarded American Cancer Society Institutional Research Grants.
American Cancer Society Institutional Research Grants are part of a block award given to UF that enables the Cancer Center to support early-stage investigations with funding. These grants help faculty initiate new research projects and obtain preliminary results needed to compete successfully for larger peer-reviewed research grants.
Applications were received from 15 UF investigators and reviewed by a committee of UF Health Cancer Center peers led by Jonathan Licht, M.D., director of the Cancer Center. Applications were scored based on their significance, innovation, approach and ability to exert an overall impact on cancer research.
Alberto Perez, Ph.D., assistant professor in the department of chemistry in the College of Liberal Arts & Sciences; Fan Zhang, Ph.D., assistant professor in the department of pharmaceutics in the College of Pharmacy; Naykky Singh Ospina, M.D., associate professor in the department of medicine, division of endocrinology, diabetes & metabolism in the College of Medicine; Zhe Ma, Ph.D., assistant professor in the department of molecular genetics & microbiology in the College of Medicine; and Ryan Kolb, Ph.D., assistant professor in the department of pathology, immunology and laboratory medicine in the College of Medicine, were selected to receive these awards.
Alberto Perez, Ph.D.
Perez will investigate the design and characterization of novel therapeutics against bromo and extraterminal domain (BET) proteins involved in lung cancer and leukemia. BET proteins are a family of proteins that regulate genetic transcription. They are characterized by two bromodomains that bind acetylated chromatin and an extraterminal domain that binds different regulatory proteins that ultimately trigger gene expression.
The overarching goal of Perez’s proposal is to develop BET inhibitors to stop oncogene expression. Most of these strategies currently in clinical trials focus on inhibiting these proteins by preventing the function of bromodomains, but Perez’s research will study the hundreds of proteins that interact with the extraterminal domain in the hope of finding new therapeutics that can stop the BET proteins involved in lung cancer and leukemia.
Fan Zhang, Ph.D.
A major obstacle for successful cancer immunotherapy is that tumor microenvironments are often hostile toward treatments and limit their efficacy. Zhang was awarded a grant to develop a specially targeted gene delivery platform to target the key suppressor cells that create hostile tumor microenvironments. Specifically, Zhang’s research will focus on targeting suppressive monocytes recruited to the tumor through chemokine (C-C motif) ligand 2 (CCL2) and its cognate receptor CCR2 (CCL2/CCR2) axis.
Currently, cancer treatments that target CCR2+ monocytes use small molecule antagonists to sequester these cells in the bone marrow. This requires repeated large doses of drugs and combination treatment with cytoreductive therapy or immunotherapies. His project seeks to change this by developing nanoparticles that can be infused intravenously and program CCR2+ monocytes to actively perform antigen-specified anti-tumor activities.
Naykky Singh Ospina, M.D.
Singh Ospina was awarded a grant for her project, titled “Factors associated with thyroid biopsy and thyroid cancer diagnosis in the state of Florida.”
According to the National Cancer Institute, thyroid cancer diagnosis rates increased the fastest among all cancers between 1975 and 2013. This increase can be partially explained by the overuse of thyroid biopsies, which can lead to unnecessary and costly medical care. At the same time, some segments of the population, such as Hispanics, are more likely to be diagnosed with later-stage cancer, suggesting an effect of access on thyroid diagnosis pathways.
Using large data sets from the OneFlorida+ Clinical Research Consortium, Singh Ospina will seek to understand the important factors in thyroid biopsy and cancer diagnosis in an effort to create better outcomes for patients. The study will examine data from 2015 to 2022 to determine ways to support better decision-making for patients with thyroid nodules.
Zhe Ma, Ph.D.
Ma will study the role of viral miRNAs in Kaposi sarcoma-associated herpesvirus (KSHV)-related malignancies. KSHV can cause lifelong infections and develop into systemic cancers with poor survival rates. The risk of developing KSHV-associated cancers is significantly higher in people who are immunocompromised, such as those with HIV infection, those who have undergone organ transplant or those of advanced age.
Previous research by Ma showed that the cGAS-STING pathway is responsible for triggering the initial immune response to KSHV infections but that KSHV establishes lifelong infections by using miRNAs to suppress cGAS-STING signaling. His research will study this process in an effort to develop new therapies.
Ryan Kolb, Ph.D.
Obesity is often associated with estrogen receptor-positive breast cancer in postmenopausal women and worse clinical outcomes regardless of menopausal status. Kolb will use his grant to study angiopoietin-like 4 (ANGPTL4)-targeted therapy and immune checkpoint inhibitors in obesity-driven breast cancer. This is a relevant cancer to the Cancer Center given that more than 70% of adults are obese in over half of the counties in the catchment area.
Previously published work by Kolb found that obesity-associated inflammation led to an upregulation of ANGPTL4 in adipocytes, which promotes breast cancer progression. He also found that lowering ANGPTL4 prevented obesity-driven breast cancer progression. His pilot project will seek novel combinatorial therapies for treating patients with breast cancer who are obese by researching ways to block ANGPTL4 in an effort to sensitize breast cancer to immune checkpoint blockade therapy.