Meet the Li Lab

For over 15 years, my scientific studies aimed to uncover the genetic basis of leukemia and lymphoma, and to discover genes that can be targets for the development of new therapeutic approaches to cancer. In 2021, I shifted to a laboratory management position, to oversee daily operations, protocol compliance, and safety. I focus on lab management while still contributing to research studies, preparation of manuscripts for publications, and grant applications. My current duties focus on the development of successful and cost-effective planning strategies while endorsing compliance with safety standards, protocol consistency, and reliability. My long-term goal is to establish a constructive laboratory environment based on teamwork and scientific collaboration, where every individual contribution aims toward a shared goal: make significant discoveries to improve the immunotherapeutic approach for the treatment of cancer.

I earned my PhD in Chemistry/Biochemistry at Miami University, where I investigated the mechanism of action of the molecular chaperone Grp94/gp96 in protein folding. In the Li lab, I extend my interest in Grp94 chaperone activity by investigating the structural and biochemical basis for the recruitment and folding of Grp94 client proteins, particularly immune-related proteins. I will leverage this knowledge to develop targeted therapies against chaperone-client interactions to improve anti-tumor immunity. I also support protein production and characterization efforts by the IMDP at the Pelotonia Research Center.

My project aims to unravel the intricate mechanisms through which gp96 modulates tumor malignancy within glioblastoma and orchestrates immunosuppressive phenotypes in microglia and regulatory T cells. Increasing evidence suggests a significant upregulation of the chaperone protein gp96 in multiple cancer types, with strong correlations to malignancy and diminished survival rates. Additionally, gp96 expression extends to various immune cell populations, exerting influence over their inherent biological functions. Of particular intrigue is uncovering the dynamic interplay between these immune cells and cancerous elements within the glioblastoma microenvironment.

Dr. Mandula received his doctoral degree in the lab of Dr. Paulo Rodriguez at Moffitt Cancer Center in 2023 where he studied the immunoregulatory role of the unfolded protein response mediator PERK in melanoma. Primary research interests include: 1) Delineating how platelets/thrombocytes and megakaryocytes exert systemic immunosuppressive priming that underwrites tumor progression and resistance to immunotherapy. 2) Interrogating the role of immunosuppressive myeloid populations in driving suppression of antitumor immunity and the development of targeted therapies to induce myeloid repolarization in the context of tumor associated Y chromosome loss. 3) Developing a comprehensive, mechanistic understanding of tumor associated cues that dictate induction versus repression of immunogenic cell death (ICD) and identifying new strategies to leverage ICD in cancer therapy.

Research Interests: Immune regulation in the tumor microenvironment, steroid hormone signaling, hormonal carcinogenesis, genitourinary oncology

I am a medical oncologist at Ohio State University with an interest in genitourinary oncology. I completed my internal medicine residency at the University of Minnesota, attended medical school at the Midwestern University Chicago College of Osteopathic Medicine, and earned a Ph.D. in Pathology at the University of Illinois at Chicago in the laboratory of Gail S. Prins, Ph.D. I am interested in understanding the molecular basis of sex differences in immune responses to cancer, hoping that this knowledge can be harnessed to improve the effectiveness of immunotherapies and adoptive cell therapies in many cancers.

Research interests: Studying the role of the zinc finger transcription factor, ZFP148, in the development and effector functions of natural killer (NK) cells.

“I earned my bachelor’s degree in Biochemistry and Molecular Biology from the College of Wooster. As an undergraduate, I participated in a summer internship at Ohio State University in Dr. Lindert’s lab, focusing on computational biology (2018-2019). In the Lindert lab, I worked on improving Rosetta’s algorithms to accurately predict and generate tertiary protein structures.

Previous bioinformatic data have identified ZFP148 as a member of the TCF1 regulatory network, whereas TCF1 promotes stemness and suppresses the terminal differentiation and exhaustion of tumor-infiltrating CD8+ T cells. Some of our unpublished data on ZFP148 regulatory role in CD8+ T cell also suggest that ZFP148 may be involved in the development and function of natural killer (NK) cells. Therefore, my goal is to elucidate the role of ZFP148 in regulating NK cell development and its effector functions in anti-tumor and anti-viral responses.”

Kelsi Reynolds is a research associate with specialized expertise in spectral flow cytometry, immune profiling, and clinical trials. As an adjacent member of the Immune Monitoring and Discovery Platform (IMDP), Kelsi provides technical expertise, advanced data analysis, troubleshooting, and training for PIIO investigators to support research in immunology and translational medicine.

Research interest: discovery of small molecules to enhance T cell stemness, with the goal of improving immunotherapeutic strategies. Additionally, platelet-specific mechanisms contributing to obesity-induced T cell exhaustion.

CD8+ T cells are essential effectors in cancer immunotherapy, yet their efficacy is often undermined by exhaustion — a state of reduced proliferation, impaired cytokine production, and diminished cytotoxicity. This phenomenon limits the success of many immunotherapeutic strategies, including immune checkpoint blockade. Restoring or enhancing CD8+ T cell stemness, a state characterized by self-renewal and multipotent potential, offers a promising avenue to overcome exhaustion and improve cancer treatment outcomes.

Research Interests: Development of logic gated CAR T-cells for next generation targeted cancer therapeutics.

Research Interest: Investigating immune cell dynamics, with a specific focus on T cell subpopulations within the tumor microenvironment.

My current research endeavors aim to deepen our understanding of T regulatory cells (Tregs) in the context of tumor immunology. Furthermore, I am involved in exploring various immunotherapeutic approaches to counteract immunosuppressive mechanisms within the tumor microenvironment.

Research Interest: Understanding T cell exhaustion to increase efficacy of immunotherapy

Current immunotherapy modalities made unprecedented improvement to cure cancer over past decades. However, not all patients respond to immunotherapy, leading us to investigate the reason why and how to overcome this limitation. Understanding the T cell exhaustion process is critical to immunotherapy related research, so we have developed a multi-spectral flow cytometry panel containing 33 markers in a mouse tumor setting. This panel comprehensively covers the T cell exhaustion process, enabling us to check the T cell state in each experimental setting. With this new technique, I will be working on understanding the complex T cell exhaustion process and identifying new strategies that can help current treatment modalities.

Research Interests: Investigating the suppressive mechanisms of regulatory T cells (Tregs) and the molecular pathways driving CD8+ T cell exhaustion in the tumor microenvironment.

I earned my bachelor’s degree in Biological Sciences from Carnegie Mellon University in Qatar. My interest in immunology began with a broader fascination with cancer and a desire to contribute to research that could lead to effective cures. This led me to explore how the immune system, particularly T cells, interacts with cancer, a rapidly evolving and impactful area of research. My current work focuses on understanding how Tregs sustain their suppressive identity and how their dysfunction influences CD8+ T cell exhaustion in tumors. We are especially interested in the role of the ER chaperone gp96 in maintaining Treg stability and suppressive function. Our findings suggest that gp96 deficiency alters Treg function. Through this work, I aim to uncover molecular mechanisms that can be targeted to improve anti-tumor immunity.

Research Interest: Mechanisms of Treg Lineage Regulation and T-Cell Tolerance in Cancer.
Dr. Velegraki’s work focuses on characterization of new mechanisms that drive Treg lineage fate as well as control Treg cell suppressive functions. Unravelling unknown physiologic processes of Treg mediated tolerance will help to better investigate the role of Tregs within the tumor microenvironment, with the long term goal being to evolve new approaches of targeting Tregs in the context of cancer immunotherapy. Maria believes that working in the laboratory stretches her commitment to serve patients outside their bedside, with the belief that this may have an even greater impact. This provides her with a surge of excitement and motivation toward scientific discovery.

Research Interest: The role of CNPY2-orchestrated unfolded protein response in T cell-mediated antitumor immunity.
Unfolded protein response (UPR) is an adaptive reaction to globally reduce unfolded or misfolded proteins accumulated in the endoplasmic reticulum (ER) when cells encounter ER stress. It is reported recently that UPR is activated in tumor-infiltrating T cells and dampens their function in the tumor microenvironment (TME). The Li Lab has discovered that CNPY2 is a key regulator upstream the PERK-branch of UPR. My work focuses on studying how CNPY2 regulates the UPR in T cells in the TME and its role in T-cell mediated anti-tumor immunity.

Research Interests – Developing effective cancer immunotherapies by targeting GARP
I am a graduate student pursuing PhD degree in cancer immunology and immunotherapy. I used to work on using the common marker CD73 to deplete major types of immunosuppressive cells to eliminate the acquired resistance in breast cancer, and I also practiced applying modified BCMA CAR-T cells to treat multiple myeloma. My current research interests center on developing effective cancer immunotherapies with targeting GARP to overcome the adaptive and acquired resistance of advanced cancers to immune checkpoint blockade (ICB) therapies, CAR-T cells, and others.

I am a 2020 Magna Cum Laude graduate from Denison University where I received my B.S. in Biology with a minor in Chemistry. I worked as an undergraduate summer researcher in 2018 and 2019 in The Ohio State University Jackman Lab through the Ohio 5 Summer Research Program. In the Jackman Lab I worked on the cloning and expression of tandem yeast Thg1 protein sequences. I am now a Research Assistant in the Li Lab where my overarching role is to manage more than 80 mouse colonies to specifically maintain strain health and regulate care costs. I also closely work with Dr. Velegraki in her investigation into targeting Tregs. I will apply to Medical School in 2022.

Research Interests – Developing CAR-Ts for hematological malignancies and solid tumors that can overcome immunosuppressive factors prohibiting higher treatment efficacy. 
Prior to starting my PhD studies I spent three years working in the biotech industry developing anti-CD19 and anti-BCMA chimeric antigen receptor T-cell (CAR-T) therapies. . I am currently supporting our novel anti-GARP CAR-T, for treatment in R/R GBM, as well as exploring further applications for this CAR by broadening its clinical scope and developing a series of dual-targeting CAR-Ts.

Research Interests: 1) Determine the genomic binding sites of androgen receptor (AR) in CD8+ T cells.
2) Dissect the role of ZFP148 and other transcription factors in regulating CD8+ T cell effector differentiation and exhaustion.
How differences in anti-tumor immunity may drive disparity in tumor incidence and mortality between sexes has not been well studied. Male sex hormone, androgen, and its receptor – androgen receptor (AR) – mediated signaling has been shown to directly drive CD8+ T cell exhaustion in the tumor microenvironment. The goal of my project is to study the downstream transcriptional regulation(s) of AR in CD8+ tumor-infiltrating lymphocytes, during which the activities of several transcription factors such as Zinc-Finger Protein 148 (ZFP148) might be involved. Understanding the above mechanisms will shed light on our understanding of sex differences in anti-tumor immunity and how sex hormones play their roles.