Research Interest: Understanding the interrelationship between coagulation and complement system and characterizing the heterogeneity of pathogenic cell population in age-related macular degeneration (AMD).
Research Aims: AMD is a complicated disease leading to irreversible, severe to total vision loss. Damage of the blood-retinal barrier, neovascularization, and deposition of C3d in the Retinal Pigment Epithelium-Bruch's Membrane (RPE/BrM) are characteristics of this disease. Coagulation factor II is a known regulator of the blood-retinal barrier destruction and vascular endothelial growth factor section. My project aim is to investigate the effects of thrombin-induced complement activation and induction of endoplasmic reticulum stress in RPE cells. Additionally, I will investigate the heterogeneity of cell populations involved in the angiogenesis, repair, fibrosis and inflammation processes in laser-induced choroidal neovascularization (CNV) model of AMD in VaV1-iCre mouse strain. To evaluate the clinical relevance of my project, we will use the electronic health records (HER) analysis approach to understand the predictive effects of coagulation factor II-inhibitor, dabigatran, on human AMD patients.
Mentor: Baerbel Rohrer, Ph.D.
Connor Dwyer, Ph.D.
Research Interests: Understanding the therapeutic benefit of Pi3Kd blockade and T cell memory differentiation on adoptive T cell therapy (ACT).
Research Aims: My Ph.D training focused on understanding how defects in T regulatory cells contributed to the development of autoimmune disorders. I intend to combine my past training with my current research to uncouple mechanisms of tolerance and immunity and improve current ACT treatment while reducing autoimmune side effects associated with many cancer therapies.
Mentor: Chrystal Paulos, Ph.D.
Stephen Iwanowycz, Ph.D.
Research Interests: Understanding chaperone regulation of dendritic cell functions in inflammation and cancer.
Research Aims: Dendritic cells (DCs) are professional antigen presenting cells, and as such they are major regulators of immunity and tolerance. Many cancer types including breast and lung cancer have been found to manipulate DCs into suppressing immune responses. We recently discovered that tolerogenic DCs are uniquely dependent on chaperone gp96 for their functions. The goal of my research is to gain a deeper understanding of tolerogenic DC regulation, and to identify the role of DCs in immune surveillance. I will characterize the anti-tumor immune response generated by genetically deleting gp96 from DCs while also seeking to develop methods to pharmacologically targeted gp96 specifically within tumor infiltrating DCs.
Mentor: Bei Liu, M.D., MPH
Khalil Mallah, Ph.D.
Research Interest: Understanding the role of complement-mediated neuroinflammation in secondary injury after Traumatic Brain Injury (TBI), and characterizing site-targeted complement inhibitors in therapeutic paradigms.
Research Aims: The complement system plays a central role in driving post-TBI inflammation. Complement activation products are involved in driving this inflammatory process, and we have shown that the complement activation product, C3d, tags injured, but still salvageable neurons, for phagocytosis by microglia. Our lab pioneered the development of site-targeted complement inhibitors, and we are investigating various strategies to deliver complement inhibitors specifically to injured brain tissue. From a therapeutic standpoint, targeted inhibitors have safety benefits since they do not systemically inhibit complement. From an investigative standpoint, these inhibitors allow us to define complement-dependent mechanisms of inflammation and injury. My project is focused on understanding the interaction between C3d-tagged neurons and microglia in both acute and chronic phases after brain injury, in addition to studying the impact of site-targeted complement inhibition on this interaction.
Mentor: Stephen Tomlinson, Ph.D.