Postdoctoral and Clinical Fellowship Awardees

Giulia Ferretti, Ph.D.

HCC Abney Fellow

Project: p53-Mediated Tumor Suppression in Liver Cancer

Mentor: Tim Barnoud, Ph.D.

"TP53 is the most frequently mutated tumor suppressor gene in human cancer. TP53 encodes a critical tumor suppressor, p53, that has many roles in protecting cells from cancer, including cell cycle arrest, senescence and apoptosis. In addition to mutations, there are naturally occurring variants in the TP53 gene known as single nucleotide polymorphisms (SNPs) that are associated with increased cancer risk in humans and mouse models.

One example of such a variant is the coding region polymorphism at amino acid 47 of p53 (Proline47Serine; hereafter S47). The S47 polymorphism of p53 is found in approximately 1-2% of African Americans. Studies in mice have shown that the S47 variant causes spontaneous tumors, with over 30% of these mice developing hepatocellular carcinoma (HCC), the most common form of liver cancer. We hypothesize that the S47 variant of p53 may be a risk factor for liver cancer in African Americans; we will test this using cell lines and mouse models of hepatocellular carcinoma. A secondary goal is to identify novel therapeutic strategies to treat tumors that contain the S47 variant of p53, a concept known as personalized medicine."

Ashvita Garg, Ph.D.

HCC Abney Fellow

Project: HPV-Related Cancer Prevention Practices and Health Behaviors Among Persons Living with HIV in a Southern HIV Care Clinic

Mentor: Ashish Deshmukh, Ph.D.

"The high prevalence of HPV is of special concern in people living with HIV (PLWHIV), as they are at a disproportionately elevated risk of developing cancers caused by HPV. This increased susceptibility to cancers necessitates the improvement of delivery and uptake of HPV-related cancer prevention methods (HPV vaccination and screening).

Although there are existing evidence-based interventions for HPV-related cancer prevention among PLWHIV, uptake and adherence remain suboptimal. Therefore, this study will help understand factors related to the uptake and adherence of HPV-related cancer prevention methods. Additionally, this study will help gain PLWHIV patient perspectives regarding the HPV vaccine and HPV-related cancer screening, which will be crucial for designing and delivering tailored interventions to improve the uptake of evidence-based cancer prevention interventions and reduce cancer burden in this vulnerable group."

Liu Liu, Ph.D.

HCC Abney Fellow

Project: The Role of PRMT2/4-Mediated Arginine Methylation in Controlling BRD4 Function in
Breast Cancer

Mentor: Wenjian Gan, Ph.D.

"Epigenetic modifications including DNA methylation and histone modifications play a critical role in several biological processes including cell proliferation, apoptosis, migration and differentiation. The bromodomain and extra-terminal domain (BET) family proteins serve as the reader of acetylated lysine and are enriched in super-enhancers/promoter region. They act as scaffolds to recruit transcription-related proteins to promote transcription.

Notably, BRD4 is the most studied BET protein and is frequently amplified or overexpressed in a variety of cancers. This study will explore how PRMT2/4-mediated methylation of BRD4 promotes its binding to acetylated histone and subsequently enhances transcription and breast cancer cell proliferation. Through these studies, we will not only expand current knowledge on the upstream regulation of BRD4, but also provide a molecular basis and rationale for combinational use of BET and PRMT inhibitors."

Alessandra Metelli, Ph.D.

HCC Abney Fellow

Project: Targeting Sphingosine 1 Phosphate Pathway in Human Myeloid Cells to Enhance Anti-Tumor Immunity During Immunotherapy

Mentor: John Wrangle, M.D.

"Macrophages are a double-edged sword in cancer therapy. On the one hand they are adaptive immune response initiators, and on the other hand they can suppress immune responses. I am interested in how the lipid immune metabolism in human macrophages can be harnessed to support anti-tumor immunity in cancer treatment. My translational project utilized human samples and single cell multi-omics approaches such as mass cytometry, RNA sequencing, and metabolism."

Vinodh Rajagopalan, Ph.D., D.V.M.

HCC Abney Fellow

Project: Allosteric Inhibition of RAS Counteracts Neuroblastoma (NBL) Tumorigenesis

Mentor: John O'Bryan, Ph.D.

"Neuroblastomas (NBL) are one of the most common pediatric solid tumors. The tumor-promoting oncoprotein called RAS is implicated in the progression of this tumor. Our lab has identified a novel inhibitor for this protein that counteracts its function. Using this novel inhibitor, we are addressing the question of whether inhibition of RAS is a viable strategy for treating NBL tumors. We are using a variety of biochemical, molecular, and cell biology approaches to answer this question. If our proposed studies are successful, our work may lead to new therapeutic strategies for treating this deadly pediatric cancer that is currently refractory to conventional therapies."

Shasha Yin, Ph.D.

HCC Abney Fellow

Project: Characterizing the Roles and Regulators of Protein Arginine Methyltransferase 5 (PRMT5) in Breast Cancer

Mentor: Wenjian Gan, Ph.D.

"Mostly breast tumors display higher PRMT5 (a coding gene) expression, and the expression levels of PRMT5 are associated with poor prognosis and survival in triple-negative breast cancer. PRMT5 is believed to function largely as an oncogene. However, the exact mechanisms by which PRMT5 promotes breast tumorigenesis are unclear. This project will dissect the mechanisms and regulations of PRMT5 in breast cancers and expect to make some groundwork for the utility of PRMT5 inhibitor in the clinic."

Jung-Hyun Cho

HCC Abney Fellow

Project: LncRNA Regulation of Glycolysis in Breast Cancer

Mentor: Je-Hyun Yoon, Ph.D.

"This research investigates the therapeutic strategy for malignant breast cancer by revealing the pivotal roles of long noncoding RNA (lncRNA) NEAT1 in glucose metabolism and cancer development. Aberrant metabolic program strongly associated with breast cancer correlates with enhanced tumorigenesis, relapse, and resistance to treatment by targeting lncRNAs. This project will provide a new therapeutic approach and help overcome resistance to treatment of malignant breast cancer."

Catherine MarElia

Project: Investigating the Role of Stromal IL-6 in the Immune Evasion and Progression of Pancreatic Cancer

Mentor: Michael Ostrowski, Ph.D.

Bartosz M. Mucha, Ph.D.

HCC Abney Fellow

Project: Dissecting an Fbxo4-hnRNPK Regulatory Axis in Oral Squamous Carcinoma

Mentor: J. Alan Diehl, Ph.D.

"Mucha’s research investigates hnRNP K, a multifunctional RNA binding protein that increases its response in many human cancers. Preliminary data revealed that hnRNP K is modified by Fbxo4-dependent ubiquitylation. The focus of his current research project is to reveal the nature of the polyubiquitin chains and the reaction of Fbxo4-dependent regulation of hnRNP K for normal versus tumor cell growth."

Benjamin R. Pryce, Ph.D.

HCC Abney Fellow

Project: NF-kB Function in Muscle Stem Cells Regulates Macrophages to Promote Cancer Cachexia

Mentor: Denis Guttridge, Ph.D.

"The goal of Pryce’s research is to explore muscle wasting in cancer, a condition called cachexia. Cachexia greatly decreases survival and quality of life in cancer patients, which is especially prominent in pancreatic cancer. His project will focus on the role of the NF-kB signaling pathway and how it contributes to cachexia in pancreatic cancer as well as other cancers."

Simon Grelet, Ph.D.

HCC Abney Fellow

Project: Transfer RNAs in Cell Plasticity and Tumor Progression: Uncharted Biology and Novel Therapeutic Avenues

Mentor: Philip Howe, Ph.D.

"The aim of Dr. Grelet's project is to decipher how tRNA biology regulates cancer invasion and stemness, two traits of the tumor cells that are deemed to be essential during tumor metastasis and tumor relapse. Such molecular insights might open new therapeutic opportunities that will be evaluated within the study."

Zongyang Lyu, Ph.D.

HCC Abney Fellow

Project: Structural Biology of the Essential Cell Cycle Regulator Cdc34

Mentor: Shaun Olsen, Ph.D.

"I study the structure and function of protein complexes in ubiquitin pathways and develop inhibitors for cancer therapeutic targets."

Yongxia Wu, Ph.D.

HCC Abney Fellow

Project: Targeting STING in Immunotherapy for Hematologic Malignancy

Mentor: Xue-Zhong Yu, M.D.

"The goal of this proposal is to define the biology of stimulator of interferon gene (STING) in immune response against leukemia after bone marrow transplantation (BMT). We will validate STING as a potential target in immunotherapy for controlling leukemia relapse and reducing the side effects associated with BMT."