PATRU: Jeffery Tomalka Lab

Assistant Professor
Pathology Advanced Translational Research Unit
Department of Pathology & Laboratory Medicine
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Dr. Tomalka received his BS in Biology from Wake Forest University in 2006. He then spent a year in the laboratory of Dr. Martha Alexander-Miller in the Department of Microbiology and Immunology at the Wake Forest School of Medicine studying the differential role of long vs. short ovalbumin peptide fragments on enhancing the avidity of antigen-specific CD4+ and CD8+ T cells. In 2007, he joined the Biological Scientist Training Program (BSTP) at Case Western Reserve University where he received his Ph.D. in Pathology in 2013. His doctoral thesis detailed the critical role for inflammasomes and TLRs in promoting protective mucosal immune responses to the fungal pathogen Candida albicans. He was the first to publish a role for the NLRP3 and NLRC4 inflammasome complexes in mediating protection from Candida infection and defined the role of these key proteins in driving neutrophil and macrophage recruitment and activation at the site of infection. He showed that the function of NLRP3 was in cells of hematopoietic origin while the function of NLRC4 was in tissue cells, providing some of the first evidence for the function of inflammasome in non-traditional immune cells. Dr. Tomalka then went on to a postdoctoral fellowship in the laboratory of Dr. Parameswaran Ramakrishnan where he studied the molecular mechanisms which govern NF-kB activation downstream of TLRs in macrophages and during Type 1 diabetes in CD4+ T cells. Notably, he was the first to demonstrate that O-GlcNAcylation, a post-translational modification in which N-Acetyl-glucosamine is added to Ser/Thr residues on proteins, of NF-kB c-Rel suppresses FOXP3 expression and Treg cell function to promote autoimmune diabetes. The mechanism of action is by reduced DNA binding of O-GlcNAcylated c-Rel to the FOXP3 promoter with simultaneously enhanced binding to T_h1 associated promoters (i.e. IL-2, IFN-g, GMCSF) providing a two-hit hypothesis for enhanced autoimmune diabetes: suppressed Treg function and augmented T_h1 function.

He joined the Sekaly Lab in 2013 where he has integrated his expertise in cellular and molecular immunology of innate immune signaling with high dimensional Systems Immunology -OMICs approaches to study the critical roles for the STING pathway and inflammasomes/IL-1 in HIV infection and vaccination. Using human cohorts of HIV infection and vaccination combined with in vitro molecular validation (cytokines, CRISPR, models of HIV infection, etc) he has clearly established that activation of the STING pathway promotes effective vaccine responses by enhancing dendritic cell and CD4+ T cells responses. STING also functions in CD4+ T cells to promote antiviral immunity and induce refractoriness to HIV infection; moreover, he has shown that activation of STING can delay HIV latency in vitro and promote differentiation of latently infected CD4+ stem cells in patients. He has also shown that heightened IL-1 and inflammasome pathway activation prior to HIV infection promotes poor disease prognosis (higher viral loads, lower CD4+ T cell counts), that IL-1b can directly enhance infection of CD4+ T cells and that this pathway can be targeted therapeutically during chronic HIV infection to ameliorate systemic immune activation.

He was recruited to Emory in 2020 as an Instructor in the PATRU to establish his independent lab. His research platform termed “Putting the T(cell) in InnaTe ImmuniTy” has four major areas of focus:

1. Innate immune induced STING/CREB1 is a mechanistic driver of protective immune responses during HIV vaccination
2. The STING/NLRX1 axis regulates acute HIV infection and latent HIV reservoir establishment/maintenance in primary CD4+ T cells
3. Heightened IL-1 and inflammasome priming prior to HIV acquisition enhances infection and viral load in people living with HIV (PWHIV) while driving CD4+ T cell death
4. Canakinumab, an IL-1b blocking antibody, reverses systemic inflammation and immune activation in PWHIV

Research Specialist
Pathology Advanced Translational Research Unit
Department of Pathology & Laboratory Medicine

Naseem graduated in 2021 from the Georgia Institute of Technology with a Bachelor’s degree in Biomedical Engineering and a Computer Science Devices minor. Naseem worked in the HBA (Human Balance Augmentation) team for two years in the EPIC (Exoskeleton & Prosthetic Intelligent Controls) lab. With a deep interest in robotic prosthetics, they performed data collection and analysis on normal human gait and recovery strategies when perturbed by pre-calculated lateral shifts of the CAREN platform. They are proficient in Python, C, Matlab, and Rstudio programming languages. Naseem’s projects at GT ranged from redesigning the bedpan, to noninvasively measuring JVP (Jugular Venous Pressure), to developing an app with Android Studio that earned an Honorable Mention in the Inventure competition. They served as a teaching assistant in Biomedical Systems and Modeling for multiple semesters.

Since joining the Tomalka Lab, Naseem has assisted Dr. Tomalka in completing key milestones, such as a large screen for STING adjuvants and RNA sequencing of blood samples from the PennVax HIV vaccine study and for Dr. Tomalka’s pilot grant through CFAR/Yerkes.

RESEARCH INTERESTS
Naseem’s enjoyment of shop work and prototype fabrication has influenced his current engagement with hands-on wet lab work, such as cell culture, nanodrop and library preparation. They continue to explore new data analysis techniques like UMAP, GSEA, & HLA-typing, and applying familiar ones in new data formats like RNA-seq, Flow Cytometry, and MesoScale proteomics. Naseem has adopted Dr. Tomalka’s interest in exploring the overlap of innate and adaptive immunity, and is fascinated with the usage of metabolomics, flow cytometry, and RNA-seq in tandem to elucidate immune pathways. Naseem is interested in learning more about Bioinformatics and seeks to apply this knowledge to user-friendly AWS pipelines, with the hope of making data analysis more accessible to other PATRU researchers.