T32 ITOS Program Fellows

Kristy Thomas, Ph.D.

Mentor: Jessica H. Hartman, Ph.D.

Project Title: Cytochrome P450 2E1 (CYP2E1) and its role in cancer metabolism

Research Interests: My research interests include nutrition, obesity, and metabolism (metabolic syndrome). My dissertation research focused on maternal and infant nutrition and metabolism. I specifically looked at maternal obesity and how maternal obesity impacts breast milk short chain fatty acid and microbiome profiles, preterm infant fecal short chain fatty acid and microbiome profiles. During my Ph.D. studies, my research focused on metabolic syndrome in several groups: female mice with alcoholic liver disease, male mice with non-alcoholic liver disease caused by the standard American diet (SAD) and men with HIV on PrEP, which has been known to cause malabsorption.

Research Aims: 
1. Determine the sensitivity of well-differentiated and poorly differentiated hepatocellular carcinoma cells expressing CYP2E1 to palmitate and iron.

2. Establish if the mechanism of cell death in hepatocellular carcinoma cells is through ferroptosis or another mechanism.

3. Compare the findings from Aims 1 and 2 to several colorectal cancer cell lines which are known to be resistant to undergoing ferroptosis.

Farah Alfatyan, Ph.D.

Mentors: Tim Barnoud, Ph.D. and David Long, Ph.D.

Project Title: Tumor extrinsic roles of HSP70 and p53 in cancer

Research Interests: Passionate about exploring the immunological basis of cancer and testing and developing effective cancer immunotherapies. My research interest lies in exploring and unravelling the complexities of the tumor microenvironment and/or the immune system.

Research Aims: HSP70 and mutant p53 have been implicated in the initiation, progression, and metastasis of a wide range of human cancers. However, the tumor extrinsic roles of these proteins have not been fully investigated. My long-term goals are to better understand the molecular mechanisms by which HSP70 and mutant p53 promote cancer by regulating the tumor microenvironment (TME) in gastrointestinal cancers, with a particular focus on pancreatic and liver cancer.

Ian Padykula, Ph.D.

Mentor: John Wrangle, M.D.

Project Title: Topical AAV-based gene therapy for the treatment of locally recurrent, surgically refractory cervical cancer

Research Interests: Investigating the trafficking of lymphoid cells to mucosal tissues in response to tumorigenesis and infectious diseases.

Research Aims: The aim of my research is to develop an AAV-vectored therapeutic for the targeted delivery of immunotherapies to cervical cancer cells. By designing payloads tailored to the mucosal tissue environment, we will leverage existing immunotherapies to better direct cytotoxic cells to solid tumors at these boundaries.

Lyndsay E. A. Young, Ph.D.

Mentor: Richard R. Drake, Ph.D.

Project Title: Advancements in glycogen detection and spatial profiling reveals a new therapeutic for Ewing sarcoma: a non-traditional glycogen storage disease

Research Interests: Investigating aberrant n-glycosylation through colorectal carcinoma progression.

Research Aims: My research focuses on elucidating the role of health disparities on altered N-glycosylation patterns in colorectal disease progression. Utilizing multimodal mass spectrometry imaging techniques, we aim to profile normal, pre-invasive lesions, adenomas, and CRC carcinoma tissue samples for facilitating translational applications and a deeper understanding of the intricate molecular landscape associated with disease progression.

Alessandra Metelli, Ph.D.

Mentor: John Wrangle, M.D.

Project Title: Biochemical and immunological study of the roles of GARP/TGF-β axis in cancer

Research Interests: Investigating the biological basis of the cancer and coagulation cross talk and designing targeted therapeutics to block the immuno-suppressive role of platelets in cancer.

Research Aims: I am studying the role of tissue factor, one key mediator of coagulation and platelet activation, in lung cancer. Tissue factor is aberrantly expressed in multiple aggressive human cancers. My research project investigates how tissue factor expressed on cancer cells and immune infiltrates enhances blood coagulation and platelet activation as part of a novel cancer immune escape mechanism.

Spencer Miller, Ph.D.

Mentor: Denis Guttridge, Ph.D.

Project Title: Purine nucleotide degradation in skeletal muscle during atrophy

Research Interests: Investigating the underlying mechanisms and consequences of inflammation in the skeletal muscle microenvironment during cancer cachexia.

Research Aims: My research aims to determine the contribution of NF-κB signaling in skeletal muscle progenitor cells to muscle atrophy during cancer cachexia. To address this aim, we are comparing the roles of NF-κB in various cell types in the muscle microenvironment using NF-κB knockout mice.

Shaaron Ochoa-Rios, Ph.D.

Mentor: Anand Mehta, D.Phil.

Project Title: Identifying the temporal N-linked glycosylation changes during liver disease progression: from liver injury to end-stage liver disease

Research Interests: My research interests are in cancer research and glycomics. My current focus is on the use of N-glycomics and mouse models for the identification of promising strategies for early diagnosis and treatment of fatty liver disease and primary liver cancer.

Research Aims: To investigate the role of Fut8/core fucosylation in vivo in early liver disease and liver cancer development.

Lillian Hsu, M.D.

Mentor: Nancy Klauber-DeMore, M.D.

Project Title: Elucidation of the role of SFRP2 in TNBC tumor immunology

Research Interests: Exploring angiogenesis factors in the development of breast cancer to improve targeted therapy and ultimately improve survival.

Research Aims: My long term goal is to care for patients with surgically resectable cancers. The project I am currently working on involves targeting a specific tumor signaling pathway with a monoclonal antibody in order to reduce tumor growth, block angiogenesis, and reduce tumor migration.

Colleen Quaas, Ph.D.

Mentor: Tim Barnoud, Ph.D.

Project Title: Regulation of chromatin modifiers during transcription and damage signaling in Xenopus egg extract

Research Interests: The impact of p53 polymorphisms and their ability to regulate p53-mediated tumor suppression.

Research Aims: My research aims to investigate the role of p53 polymorphisms in the context of the DNA damage response and its impact on tumor suppression. Additionally, I will explore the role of novel HSP inhibitors and their effects on gastrointestinal cancers, with a specific focus in pancreatic malignancies.

Samaneh Saberi, Ph.D.

Mentor: Michael Ostrowski, Ph.D.

Project Title: Depiction of the time‐map of the molecular cascade of gastric intestinalization caused by Helicobacter pylori infection via tracing key biomarkers in vitro and in vivo

Research Interests: Interrogate the function of STAT3 in tumor fibroblasts during PDAC progression and cachexia.

Research Aims: My research aims to characterize changes in the tumor microenvironment when STAT3 is ablated in cancer associated fibroblasts in the cancer mice PDAC model. To gain this aim, we are going to compare STAT3-dependent transcriptomes in CAFS and FAPs to identify common STAT3 targets in the tumor macroenvironment.

Bernice Agana, Ph.D.

Mentor: Lauren Ball, Ph.D.

Research Interests: Role of O-GlcNAcome in breast cancer initiation, proliferation, and metastasis.

Research Aims: The OGT interactome and O-GlcNAcome between cancer cells and cancer stem cells will be compared using quantitative proteomics. My research aim is to identify novel signaling networks, probe the potential interplay of Ser/Thr O-GlcNAcylation and phosphorylation, and reveal regulators of tumor-initiating ability.

Alex Andrews, Ph.D.

Mentor: Jessica Thaxton, Ph.D.

Research Interests: The impact of tumor microenvironment stress on T-cell metabolism and function in cancer immunotherapy.

Research Aims: My research investigates the role of endoplasmic reticulum (ER) stress sensor PKR-ER like kinase (PERK) and its ability to modulate T-cell metabolism in response to tumor microenvironment stress, with the goal of enhancing cancer immunotherapies.

James Atkison, Ph.D.

Mentor: Shaun Olsen, Ph.D.

Research Interests: Investigation of the structure and role of the nephila clavipes major ampullate spidroin 1A N-terminal domain.

Research Aims: My long-term career goal is to work in the biomedical industry and discover life saving devices and drugs to be used in cancer therapies. I hope to contribute to the ever-growing field of cancer therapeutics by investigating small molecule interactions for future drug development.

Andrew Baldwin, Ph.D.

Mentor: David Turner, Ph.D.

Research Interests: The influence of dietary advanced glycation end products on breast and prostate cancer microenvironments and tumor development.

Research Aims: My research focuses on the role dietary advanced glycation end products play in the formation of tumor promoting microenvironments in breast and prostate tissue, with the goal of inhibiting dietary availability of AGEs to reduce their accumulation in the body and prevent disease development.

Annamarie Dalton, Ph.D.

Mentor: Philip Howe, Ph.D.

Research Interests: Interleukin-like EMT inducer (ILEI) signaling in metastatic breast cancer

Research Aims: Previously, my research focused on structural and biophysical characterization of the Tie2 endothelial specific receptor. Through the ITOS program, I hope to integrate techniques learned during my Ph.D. training with in-depth signaling evaluation in vivo to further knowledge in breast cancer pathobiology.

Toros Dincman, M.D., Ph.D.

Mentor: Philip Howe, Ph.D.

Research Interests: Evaluating interleukin-like EMT inducer's (ILEI) role in therapeutic sensitivity in lung cancer.

Research Aims: My research aims are to further our understanding on cancer pathogenesis and identify clinically applicable treatment paradigms in hopes of improving patient survival.

Nancy Echeverri-Ruiz, Ph.D.

Mentor: David Long, Ph.D.

Research Interests: Understanding how BRCA1's role in transcription regulation influences genome integrity and cancer development.

Research Aims: My project seeks to extend our recent biochemical observations into human cell-based models. We've identified a new relationship between an established tumor suppressor (BRCA1) and an emerging player in cancer development (BRD4). My goal is to understand how BRCA1 regulates BRD4-dependent transcription and the effect it has on expression of major oncogenes. This work has specific ties to hypoxia, which may promote loss of BRCA1 and concomitant increase in BRD4 activity.

Denise Garcia, M.D.

Mentor: Nancy Klauber-DeMore, M.D.

Research Interests: Development of alternate cancer immunotherapies in aggressive and therapy-resistant cancers.

Research Aims: My research will investigate the efficacy of novel alternative immunotherapies in aggressive cancer treatment and their mechanisms of action with regards to the tumor signaling pathway. I will also investigate the impact of combination immunotherapies on cancer growth, proliferation, and invasion.

Lu Han, Ph.D.

Mentor: Michael Ostrowski, Ph.D.

Research Interests: Cellular Interaction and Coordination between Epithelium and Mesenchyme during Development and Cancer.

Research Aims: My research aims to develop innovative perspectives to exploit the similarities and tease apart the differences between the embryonic developmental processes and cancer progression. With a particular interest in the tissue resident fibroblast, I aim to uncover novel cellular interactions in the tumor microenvironment, which ultimately could serve as therapeutic targets.

Stephen Iwanowycz, Ph.D.

Mentor: Bei Liu, M.D.

Research Interests: Role of innate immune cells in the tumor microenvironment.

Research Aims: I am passionate about using science to advance precision medicine. I would like to build my research around investigating the signaling between the different cell types within tumors in order to develop targeted therapies to reverse immune suppression.

Catherine MarElia, Ph.D.

Mentor:  Michael Ostrowski, Ph.D.

Research Interests: Elucidating mechanisms of stromal fibroblasts’ impact on tumor cells in pancreatic cancer.

Research Aims: The aim of my research is to interrogate the effects of conditional expression of important signaling pathway members, such as IL-6, within the stromal fibroblasts on tumor cells to gain insight into the disparate pathophysiological effects of spatially distinct expression of these effectors during the progression of pancreatic adenocarcinoma.

Lawton Roberts, Ph.D.

Mentor: J. Alan Diehl, Ph.D.

Research Interests: The unfolded protein response (UPR) and sphingolipid metabolism in cancer cell biology.

Research Aims: As my research focus is in cancer cell biology, I aim to use cancer cell models and rodents, genetic techniques/manipulation, and confocal microcopy to address compelling questions in cancer biology research in an effort to specifically understand the effects of mycobacterium tuberculosis and interleukin-27 on human dendritic cells.

Reeder Robinson, Ph.D.

Mentor: Nathan Dolloff, Ph.D.

Research Interests: Development of experimental therapeutics against multiple myeloma.

Research Aims: My research aims are to discover the target of our lead experimental compound E61, a compound that is synergistic with proteasome inhibitors in Multiple Myeloma, and to develop a more efficacious and metabolically stable derivative that we can move into clinical trials.

Kelly Wolfe, Ph.D.

Mentor: David Long, Ph.D.

Research Interests: Ubiquitin Signaling during DNA Interstrand Crosslink Repair.

Research Aims: Defects in interstrand crosslink repair can lead to Fanconi Anemia and hereditary breast and ovarian cancers. My research will explore how ICL repair is influenced by atypical ubiquitin linkages and use basic biology to provide insight into human health and disease.

Stephen Zambrzycki, Ph.D.

Mentor: Peggi Angel, Ph.D.

Research Interests: The influence of race-dependent collagen sequence variants in tumorigenic signaling through integrated biological assays and mass spectrometry imaging.

Research Aims: The aim of my research is to demonstrate that collagen sequence variants due to proline hydroxylation have functional effects on oncogenic signaling. We will explore how ancestry dependent proline hydroxylation of collagen may increase tumorigenic signaling in breast cancer.