Center Events

Nicholas Pokorzynski, PhD - Postdoctoral Research Associate, Department of Microbial Pathogenesis, Yale University School of Medicine

Abstract: Glucose is the preferred carbon source of most microorganisms. Why, then, does glucose lose its preferred status when the intracellular pathogen Salmonella enterica serovar Typhimurium is inside mammalian macrophages? We now establish that this surprising behavior results from macrophages provoking cytoplasmic Mg2+ starvation in S. Typhimurirum. Cytoplasmic Mg2+ starvation drastically reduces synthesis of cyclic adenosine monophosphate (cAMP), the allosteric activator of the cAMP receptor protein (CRP), master regulator of carbon utilization. The resulting reduction in cAMP concentration decreases transcription of CRP-cAMP-activated carbon utilization determinants, which reduces uptake of corresponding carbon sources and modifies metabolism. Rendering CRP activity cAMP independent or supplementation with exogenous cAMP overcomes transcriptional, transport, and metabolic restrictions caused by cytoplasmic Mg2+ starvation. S. Typhimurium’s reduced glucose preference inside macrophages reflects that transcription of the glucose uptake gene is far more sensitive to the amount of active CRP protein than transcription of other carbon uptake genes. By reducing CRP-cAMP activity, the intramacrophage environment restricts S. Typhimurium metabolism, consistent with decreased protein synthesis that slows pathogen growth, heightening tolerance to antimicrobial agents.

Zoom: https://urmc.zoom.us/j/94337654366?pwd=pezThiio47PqoHmC4aTy5bflDnEovb.1

Passcode: 051922

 Oct 14, 2024 @ 12:00 p.m.

 Medical Center | K307 (3-6408)

Maggie Lesch - PhD Candidate, Immunology, Microbiology, and Virology Ph.D. Program

Colorectal cancer (CRC) is a devastating malignancy that ranks as the second leading cause of cancer-related deaths, and fourth in cancer diagnoses annually in the United States. Among CRC cases, rectal cancer (RC) comprises one-third of cases, with over 50,000 people in the US diagnosed each year. Surgical resection is a treatment option for RC, however it can greatly reduce patients’ quality of life and unfortunately, some patients still experience recurrence. Recently, treatment paradigms have shifted towards organ preservation in RC through the adoption of the watch-and-wait approach in which patients undergo total neoadjuvant treatment with active surveillance, often avoiding surgery. While approximately 30% of patients experience a complete clinical response with this approach, most have an incomplete response to neoadjuvant therapy and ultimately require surgery or further therapy. Why this binary divide occurs is poorly understood, and there are no biomarkers for predicting response. To study this question, our lab has developed a clinically relevant orthotopic murine model of RC, in which administration of Short Course Radiation Therapy (SCRT) results in recapitulation of this binary responder/nonresponder phenotype seen in patients. Our model enables the study of both phenotypes during and following treatment. Using this model, we performed a series of experiments to investigate the molecular mechanisms driving this responder/nonresponder dichotomy. Specifically, RNA-sequencing of intratumoral cell populations, following SCRT, revealed an upregulation of the Type I Interferon (IFN) signaling pathway in responder tumors when compared to nonresponders. Type I IFNs have emerged as essential cytokines that mediate the antitumor immune response. Preliminary data has confirmed that responder tumors had higher concentrations of intratumoral Type I IFN protein that were maintained throughout treatment. Blockade of the Type I IFN receptors completely abrogated the responder phenotype further emphasizing the importance of these factors in dictating the responder/nonresponder divide. To explore what may mediate this effect, we investigated the influence of the microbiome, as pathogen associated molecular patterns (PAMPs) from radio-sensitive bacteria are known to contribute to Type I IFN production. To test this, we depleted the microbiota by administering antibiotics throughout SCRT treatment. This resulted in a decrease in responder tumors, indicating that the microbiome plays a significant role in mediating the therapeutic effect. Future experiments using fecal transplants and 16s sequencing will explore whether specific bacteria or subsets of bacteria govern the treatment response. These studies are clinically translatable and may identify noninvasive predictive biomarkers, with the potential to improve the efficacy of SCRT and increase the number of patients who respond to treatment.

 Oct 10, 2024 @ 12:00 p.m.

 Medical Center | K307 (3-6408)

Host: Advisor: Scott Gerber, PhD

Kumari “Kavita” Thakur, PhD - Associate Research Scientist, Division of Molecular, Cellular and Development Biology, Yale University

Abstract: Bacteria are equipped with intricate mechanisms to adapt to environmental stresses, many of which involve non-coding RNAs such as small RNAs (sRNAs) and riboswitches. These regulatory RNAs play pivotal roles in bacterial virulence, biofilm formation, and antibiotic resistance. My research focuses on unraveling the post-transcriptional regulation of gene expression in bacteria, especially through noncoding RNA-based mechanisms. I will discuss my recent work on the role of sRNAs and RNA-binding proteins, such as Hfq, in regulating bacterial responses to stress. I will highlight my discoveries on the role of intrinsically disordered domains in Hfq, a previously debated topic in the literature, which are crucial for RNA interactions and gene regulation. Additionally, I will present the discovery of a novel riboswitch that detects 8-oxoG, a product of bacterial DNA damage caused by oxidative stress, leading to gene regulation. These findings were investigated using a variety of in vivo and in vitro techniques, including genetic reporter fusions assays, RNA sequencing (RNA-seq), northern blotting, and in-line probing assays. Join us to explore the critical role of non-coding RNAs (sRNAs and riboswitches) in the regulation of gene expression and their impact in the coding world of bacteria.

Zoom: https://urmc.zoom.us/j/99319220852?pwd=IIXdtQikGkNO905Rm1flLoXnjZISK4.1

Passcode: 717782

 Oct 10, 2024 @ 10:00 a.m.

 Medical Center | K307 (3-6408)

Robert J. Binder, PhD - Professor, Department of Immunology, University of Pittsburgh

During cancer immunosurveillance, dendritic cells (DCs) play a central role in orchestrating T cell responses against emerging tumors. Capture of miniscule amounts of antigen along with tumor-derived costimulatory signals can drive maturation and activation of DCs. We have shown that expression of the heat shock protein receptor CD91 on DCs is essential in the cross-priming of T cell responses in the context of nascent tumors. In this presentation, the mechanisms of the HSP-CD91 pathway will be laid out in mouse and human disease, as well as novel approaches to cancer immunotherapy borne out of our findings.

 Oct 07, 2024 @ 12:00 p.m.

 Medical Center | Upper Auditorium (3-7619)

Host: Jacques Robert, PhD

Dr. Sang Lee, PhD - Faculty Candidate

 Oct 04, 2024 @ 12:30 p.m.

 Kornberg Medical Research Building | 3.9654

Host: Tim Mosmann, PhD

Taylor Jones - Graduate Student

Influenza is a respiratory virus that infects the airways and lungs. Viral replication in the lower respiratory tract can result in pneumonia and severe disease. Immunological memory established by prior infection, such as T cells resident in the tissue, or vaccination significantly reduces virus-related morbidity and mortality. Although tissue-resident memory CD8 T cells (TRM) can rapidly mobilize upon reinfection to prevent disease severity, vaccine platforms often overlook cellular responses. We aim to uncover how TRM develop and understand what regulates their retention. TRM are a memory T cell subset that remain in the tissues and do not recirculate. Human and mouse TRM can express the integrins CD49a/CD29 and CD103/B7, which bind to local lung ligands and can be induced by TGFb and IL-12.

CD49a is indispensable for TRM retention; however, less is known about where and when CD49a becomes necessary during the T-cell response. We have shown that by day 8 in the lungs, CD49a- populations decreased, while the CD49a+ continued to increase. Because CD49a function may be important during the acute phase, we first wanted to understand where and when TRM precursors are formed. We measured CD49a and CD103 expression in WT mice in the priming lymph node (mediastinal lymph node: mLN) between 4-6 days post influenza A infection. This revealed that CD49a and CD103 are detected as early as 5 DPI, indicating that signals in the mLN promote TRM integrin expression. We addressed whether the activated T cells in the mLN were destined to traffic to the lungs. Blocking mLN egress with FTY720 reduced flu-specific CD49a+ populations in the lungs. This indicated that the mLN is a source of flu-specific integrin-positive cells in the lungs.

Given that CD49a-expressing cells are primed during early infection, we determined if CD49a is required for lung retention during the memory phase. We developed a tamoxifen-inducible knockout model (iKO) to target CD49a specifically in CD8 T Cells. With this model, we found that CD49a gene deletion reduced frequencies of CD49a expression in iKO mice; however, these CD49a- cells were still detectable in the lungs 6 days after inducing gene deletion. From these experiments, we hypothesize that CD49a expression is induced during the acute phase and supports retention before the memory phase. Understanding how TRM are formed and retained can inform vaccine design and help produce sustained tissue-resident and cross-protective T cells.

 Oct 03, 2024 @ 12:00 p.m.

 Medical Center | K307 (3-6408)

Host: Advisor: David Topham, PhD

Aoshu Zhong, PhD - Postdoctoral Fellow, Division of Molecular and Cellular Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Bethesda, MD

Abstract: Research into bacterial immunity has led to the discovery of critical tools for molecular biology, including restriction enzymes and CRISPR systems. In this seminar, I will discuss the characterization of a novel family of antiphage defense proteins in bacteria and archaea whose toxic activities are blocked by antitoxin proteins encoded within the same genes. Specifically, I discovered that the broadly distributed recombination-promoting nuclease (rpn) genes uniquely encode two proteins. The Rpn long proteins are toxic, while the variable C-terminal domains, which are translated separately, function as the antitoxin. Moreover, I found that the C-termini of the Rpn proteins contain unique four amino acid repeats whose number can vary widely across strains of the same species. I solved the first crystal structure of an Rpn family protein. Finally, I demonstrated Rpn proteins provide resistance to phages. I propose that many more intragenic-encoded proteins that serve regulatory roles remain to be discovered in all organisms.

Zoom Passcode: 087445

 Sep 30, 2024 @ 12:00 p.m.

 Medical Center | K307 (3-6408)

Molly Niska - Graduate Student

Generating an antigen-specific memory B cell (MBC) pool upon antigenic exposure is an essential component of the adaptive immune response. A proportion of MBCs generated in responding lymph nodes during an immune response enter the circulation and disperse to lymphoid tissues throughout the body. Due to its size and cellularity, the spleen has long been recognized as a reservoir of MBCs, but recent studies implicate a novel functional role. Recent analysis of the B cell receptor (BCR) repertoire through phylogenetic reconstruction revealed distinctive patterns of BCR clonality in circulating MBCs compared to spleen-resident MBCs. While all circulating MBCs had clonally related precursors in the spleen, the splenic MBC reservoir contained unique clones absent in the circulation. Based on this finding, the idea that the spleen “archives” MBC clones generated in past responses was proposed. Expanding this idea, we suggest that the spleen is a dynamic archive accumulating antigen-reactive MBCs reactive to past infections and maintaining clonal families across multiple MBC subsets. This is supported by recent studies describing phenotypically and functionally distinct splenic MBC subsets, such as a CD21hi MBC subset in the splenic marginal zone with enhanced responsiveness to activation and a spleen-resident population of self-renewing T-bethi MBCs.

Here, we interrogate hemagglutinin-reactive splenic MBC subsets and characterize their properties and contributions to anti-influenza immunity. We chose HA as a model antigen as this enables us to capture the dynamics of HA-specific MBC in the spleen, owing to the chronological circulation of influenza A strains in human populations. Furthermore, repeated exposure to HA adds another complexity to our analysis of the splenic MBC archive, as MBCs with certain HA reactivities may reveal unique phenotypic and functional features. Using an extensive flow cytometry panel consisting of both surface markers and HA probes, we identified the phenotypic subsets in which HA-reactive MBCs reside. Strikingly, most MBCs reactive to early-life HA probes were confined to the T-bet hi spleen resident, self-renewing population. Contrastingly, MBCs reactive to more recently circulating HAs were primarily found in the CD21hi compartment, poised for rapid response to re-exposure. The archive hypothesis was further reinforced upon evaluation of Ab reactivity, demonstrating retention of MBC reactivities across a broad range of HA vintages. Thus, we suggest the spleen is a dynamic archive, selectively preserving MBCs reactive to no longer circulating influenzas, while continuously accruing MBCs to circulating influenza A viruses. Moreover, the functional compartment where MBCs of different reactivities reside might reflect the breadth of HA reactivity and frequent or recent activation and expansion. By improving our understanding of MBC maintenance, we will be better suited to design and evaluate the effectiveness of vaccine candidates based on key biomarkers of durable, long-lasting immune memory.

 Sep 26, 2024 @ 12:00 p.m.

 Medical Center | K307 (3-6408)

Host: Advisors: Martin Zand, MD, PhD and Tim Mosmann, PhD

Pu-Ting Dong, PhD - NIH/NIDCR K99 Postdoctoral Fellow, The ADA Forsyth Institute, Harvard University Cambridge, MA

Abstract: Optical imaging techniques, such as label-free chemical imaging and fluorescence in-situ hybridization (FISH), have emerged as indispensable tools for unraveling the complexity of polymicrobial communities. Label-free chemical imaging enables non-invasive, high-resolution visualization of molecular composition, providing insights into spatial and temporal metabolic activities without the need for exogenous markers. Complementing this, fluorescence in-situ hybridization facilitates the precise localization of specific nucleic acid sequences within cells, allowing for the targeted examination of genomic elements and microbial identification. My research will delve into the synergistic application of both label-free chemical imaging and next-generation multiplex FISH imaging, to offer a comprehensive perspective on the functional analyses of biological systems. The integration of these techniques will not only advance our understanding of cellular dynamics but also holds promise for diagnostic and therapeutic innovations in diverse biological research and clinical contexts.

Zoom Passcode: 396091

 Sep 23, 2024 @ 12:00 p.m.

 Medical Center | K307 (3-6408)

Zachary Boodoo - Graduate Student

Even on combined antiretroviral therapy (cART), people living with HIV (PLWH) experience a low level of viral replication that engenders a chronic inflammatory state and increases their risk to develop multiple types of vascular disease. Previous work by our lab has demonstrated platelet-monocyte complexes (PMCs) occur with greater frequency in PLWH due to aberrant platelet activation, and these complexes are associated with higher expression of monocyte activation markers, as well as pro-inflammatory CD16+ intermediate and non-classical monocyte (NCM) phenotypes. However, the fate of PMCs in the vascular disease microenvironment, and the platelet-induced transcriptional networks that lead to cellular dysfunction, are not well characterized.

Considering these unknown entities, we implemented a study cohort to investigate the effects of chronic HIV infection on vascular disease (atherosclerosis). Participants were age-, sex-, and Reynolds risk score-matched and divided into four subgroups based on their HIV and AS status (HIV-AS-, HIV+AS-, HIV-AS+, and HIV+AS+) (n=32). Monocytes were isolated from participant PBMC or whole blood samples via flow-activated cell sorting (FACS) and analyzed by single cell RNA sequencing (scRNA-seq). Unbiased clustering revealed 10 monocyte subsets that were conserved across participants groups, two of which were identified as PMCs based on an enrichment of platelet-associated transcripts. Differential gene expression (DGE) analysis of PMCs in PLWH and AS together compared to people living with AS (PLWAS) alone revealed an upregulation of genes involved inflammatory responses (antigen processing and presentation, chemokine signaling pathway), lipid metabolism (arachidonic acid metabolism, ABC transporters, alpha linoleic acid metabolism), and cardiovascular function (cardiac muscle contraction, arrhythmogenic right ventricular cardiomyopathy). Mass spectrometry of participant plasma samples revealed differentially abundant proteins associated with vascular disease processes. Stabilin-1, a macrophage and endothelial cell scavenger receptor with atheroprotective effects, and angiopoietin-like 4 (ANGPLT4), a pro-resolving factor in an inflamed intima environment, were less abundant or entirely absent in the plasma of HIV+AS+ participants compared to those who are single-afflicted or healthy controls. Myotrophin, a myocardial hypertrophy-inducing factor elevated in people who have experienced heart failure, and serum amyloid A2, a well-characterized local mediator of atherosclerosis and vascular dysfunction, were elevated in HIV+AS+ participants.

Oxidized lipoprotein (oxLDL), a key mediator of atherosclerosis, has been demonstrated to incur epigenetic changes in monocytes that alter its response to future inflammatory stimuli. To determine the effect of platelet interactions on this trained immunity paradigm, monocytes and collagen-activated platelets were cocultured for seven days with or without oxLDL, and stimulated with LPS at day six. Flow cytometric analysis of monocyte-derived macrophages revealed that platelet interactions decreased CD36 (scavenger receptor) and CD14 expression, and increased expression of antigen-presentation molecule CD86. CD40 expression was similar between non-PMCs and PMCs, but LPS-stimulation reduced expression in PMCs relative to non-PMCs. Collectively, these results demonstrate that platelets alter monocyte-macrophage phenotypes, and PMC gene signatures in PLWH and AS are proinflammatory. In-depth understanding of platelet-mediated monocyte dysfunction in HIV infection can pave the way to develop potential therapeutic approaches to address viral-associated vascular disease and related comorbidities

 Sep 19, 2024 @ 12:00 p.m.

 Medical Center | K307 (3-6408)

Host: Advisors: Meera Singh, PhD and Juilee Thakar, PhD

Yuchang Liu - Graduate Student

Antibiotic resistance has been an increasing global health issue, and the spreading of antibiotic resistance will lead to the emergence of multi-drug resistance bacteria. While conjugation is one of the most important ways of spreading antibiotic resistance, separate plasmid transfer events always exhibit different efficiencies. Right now, the literature consensus believes that recipient strains will not play a large role in dictating conjugation efficiencies, but all the previous studies just used KO or mutant libraries of the same parent strain, which can only induce low genetic diversity. Hence, there is a gap in our mechanistic understanding of recipient-specific features that impact conjugation efficiency. However, due to the genetic differences between different strains, they will probably build up different conditions and barriers for the plasmids, and thus show different abilities to receive the plasmids. In addition, we collected more than 30 drug-susceptible Klebsiella pneumoniae isolates, and found their abilities to receive plasmids are significantly different. We aim to explore the factors that determine an optimal plasmid recipient in the genetic aspect. Currently, we have found several potential gene clusters that might contribute to the high conjugation efficiency phenotype through a functional genomic screen. We also have verified that the insertion of some of these potential genes will make a difference in the conjugation efficiency. In the future, we will also try to find out the genes that contribute to the low conjugation efficiency.

 Sep 12, 2024 @ 12:30 p.m.

 Medical Center | K307 (3-6408)

Host: Advisor: Allison Lopatkin, PhD

Chenghao Wang - Graduate Student

Toxoplasma is a common intracellular parasite that can infect almost all nucleated cells. Innate immune recognition of this pathogen leads to the production of chemokines and IL-12, which are crucial for host resistance to the parasite. We have previously defined the key steps involved in T. gondii recognition in the mouse system and identified TLR11 as a major innate immune sensor that recognizes T. gondii profilin and triggers a potent MyD88-dependent IL-12 response essential for host resistance.

Additionally, we recently revealed that the production of CCL2 by mouse and human cells is central to regulating immunity to T. gondii. We and others have shown that this response can be induced via TLR11-dependent and independent mechanisms, with the TLR11-independent release of the human alarmin S100A11 contributing to CCL2 production. In my work, I identified that, in addition to proteins, the release of lipids from T. gondii-infected human cells plays a role in the induction of CCL2 by monocytes. Furthermore, different T. gondii virulence factors may influence the parasite's recognition by human cells and the lipid-mediated induction of CCL2. The current work is focused on the molecular mechanisms responsible for the release of lipids during T. gondii infection of human cells.

 Sep 12, 2024 @ 12:00 p.m.

 Medical Center | K307 (3-6408)

Host: Advisor: Felix Yarovinsky, MD

Imtiaz A. Khan, PhD - Professor of Microbiology, Immunology, and Tropical Medicine, George Washington School of Medicine & Health Sciences

Toxoplasma gondii is a major food-borne illness that causes severe disease in humans, especially newborns and immunocompromised individuals. CD8 T cell immunity is critical for keeping chronic infection under control, During later phases of chronic infection, CD8+ T cells develop exhaustion which compromises long-term immunity against the parasite, causing reactivation of latent infection. Maintenance of functional memory CD8 population is highly essential for host survival and it is critical to understand the mechanism by which this response can be achieved. Data from our laboratory demonstrates that CD8 T cell response is comprised of heterogenous population including one effector and three memory populations. The process is complex and individual contribution of memory subsets in the generation of effector response need to be studied.

 Sep 09, 2024 @ 12:00 p.m.

 Medical Center | Upper Aud. (3-7619)

Host: Felix Yarovinsky

Lauren Paddock - Graduate Student

Obesity-related type 2 diabetes (obesity/T2D) is associated with a dysbiotic gut microbiome, chronic inflammation, and impaired adaptive and innate immunity that increases the risk of severe bacterial infections. Previous research in our lab has shown that supplementation with the dietary fiber oligofructose (OF) reduces the severity of Staphylococcus aureus osteomyelitis in a mouse model of obesity/T2D, as well as partially correcting the gut microbiota to a homeostatic state with an increase in beneficial bacteria. However, our understanding of the mechanisms by which modifications of the gut microbiota and diabetic microenvironment alter host infection responses are limited. Metabolite analysis of the oligofructose supplemented obese/T2D mice revealed elevated levels of polyamines, immunomodulatory metabolites synthesized by the gut microbiota and the host. Although polyamines are a common metabolite of the gut microbiota, the bacterial community that contributes to polyamine biosynthesis remains unclear. We found that the increased levels of polyamines locally in the gut and systemically in the plasma correlated with a higher abundance of Bifidobacterium pseudolongum, indicating that this member of the gut microbiota may contribute to increased production of polyamines. Other investigators have shown that Enterococcus faecalis contributes to production of polyamine through a symbiotic association with other gut bacteria and integration of polyamine biosynthesis pathways across multiple taxa. To identify additional bacteria in the oligofructose supplemented mice that contribute to polyamine biosynthesis, we isolated representative bacterial taxa from mouse fecal material and screened for production of polyamines. Isolates from each of four taxa, B. pseudolongum, Lactobacillus johnsonii, Staphylococcus epidermidis, and Enterococcus faecalis produced varying levels of polyamines, suggesting strain specific polyamine biosynthesis. We have sequenced the complete genomes of these isolates to further determine the pathways and potential regulatory mechanisms of polyamine biosynthesis in these species. Further in vitro co-culture experiments, along with untargeted metabolomic analyses, will identify potential symbiotic interactions between these species that contribute to host response and coordinated production of polyamines and other metabolites that modulate the immune response to infection.

 Sep 05, 2024 @ 12:30 p.m.

 Medical Center | K307 (3-6408)

Host: Advisor: Steven Gill, PhD

Thomas Wilson - Graduate Student

A recent resurgence of poxvirus infections around the world has renewed the need for improved vaccines and anti-viral treatments for these viruses. Clade-1 Monkeypox has been named a public health emergency with an increase in spread outside of Africa. This resurgence highlights major knowledge gaps in our understanding of this family of medically important viruses. Among these is the lack of a widely accepted and confirmed cellular receptor(s). With multiple receptors proposed, a more direct approach is required. Here, we propose the use of yeast display to interrogate putative proteins as receptors for the prototypical poxvirus, vaccinia. Yeast do not natively interact with vaccinia virus and carry out post-translational modifications that are similar to mammalian cells. Currently we have integrated several potential receptors into a yeast display system and are verifying their expression and native conformation. This will allow us test fluorescent virion binding via yeast pull-downs. Flow cytometry will be used to confirm binding and quantify the affinity of any potential interactions. Identification of cellular receptors for poxviruses should allow for the development of better drugs and antibodies that target specific virion proteins that are involved in poxvirus binding and entry.

 Sep 05, 2024 @ 12:00 p.m.

 Medical Center | K307 (3-6408)

Host: Advisor: Brian Ward, PhD

Jennifer Nicholson - Graduate Student

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease affecting multiple organ systems. Lupus nephritis (LN) is one of the most common and severe clinical manifestations of SLE, resulting in kidney damage and impaired kidney function. Currently, therapies for SLE are aimed at reducing immune activation rather than treating chronicity and tissue damage. Sodium glucose cotransporter 2 (SGLT2) inhibitors are a promising treatment option to address this unmet need. Originally approved for use in type 2 diabetes, SGLT2i have improved renal outcomes in patients with chronic kidney disease from multiple etiologies. Interestingly, SGLT2i have recently been shown to reduce cellular senescence in the kidneys of diabetic mice. However, the mechanisms underlying the reno-protective effects of SGLT2i are still unclear and have yet to be investigated in LN. Preliminary data from our lab shows a decrease in kidney fibrosis, autoantibody secreting cells, and cystatin C—a marker of kidney damage—in lupus-prone mice after treatment with SGLT2i. Recently, cellular senescence has been described in the LN kidney. Elevated levels of p16INK4a, a cell cycle arrest protein frequently used as a marker of senescence, were detected in kidney tissues of human LN patients and correlated with disease severity. Additionally, we have demonstrated an increase in p16INK4a, γH2AX, and other senescence markers in the kidneys of NZB/W lupus-prone mice. There are several key questions remaining to be addressed, including the relationship between senescence and disease severity, cell types affected, and contribution to disease pathology. To begin to address these questions, we will leverage existing kidney tissues from NZB/W mice at a variety of ages and disease stages and utilize immunohistochemistry to detect the presence of different senescence markers. NZB/W mice will be treated with SGLT2i, and the impact on senescence markers, kidney damage, and immunopathology will be evaluated via IHC and qPCR. Our study may help define the role of cellular senescence in LN and support the use of SGLT2i as a novel therapeutic option in LN.

 Aug 29, 2024 @ 12:00 p.m.

 Medical Center | K-307 (3-6408)

Host: Microbiology and Immunology Student Seminar
Advisor: Jennifer Anolik, MD, PhD

Amelia M. Knudsen-Clark, MS - PhD Candidate

 Aug 26, 2024 @ 12:00 p.m.

 Medical Center | K-207 (2-6408)

Host: Advisors: Brian J. Altman, PhD and Minsoo Kim, PhD

Tentative Itinerary

Please RSVP by Friday August 9^th

 Aug 23, 2024 @ 8:00 a.m.

 Helen Wood Hall | Aud 304

Tara Vrooman - PhD Candidate, Immunology, Microbiology and Virology PhD Program

 Jul 30, 2024 @ 10:00 a.m.

 Medical Center | K-207 (2-6408)

Host: Advisor: Scott Gerber, PhD

Joshua W. Modell, PhD - Assistant Professor of Molecular Biology & Genetics, Johns Hopkins University School of Medicine

CRISPR-Cas systems provide bacteria with adaptive immunity against bacteriophages and other foreign genetic elements. However, there is a growing appreciation that overexpression of CRISPR-Cas components is toxic in both their native hosts and heterologous systems for gene editing. In this seminar, I will discuss the S. pyogenes CRISPR-Cas9 system and describe how it is (i) transcriptionally repressed to mitigate autoimmune toxicity in the absence of phage and (ii) rapidly induced in the presence of phage to promote bacterial survival.

 Jun 10, 2024 @ 12:00 p.m.

 Medical Center | Upper Auditorium (3-7619)

Host: Dept. Microbiology & Immunology Seminar Series and Andrew Varble, PhD

Kala Hardy, MS - PhD Candidate, Immunology, Microbiology and Virology PhD Program

 Jun 10, 2024 @ 10:00 a.m.

 Medical Center | K-207 (2-6408)

Host: Advisor: Toru Takimoto, PhD

Anushka Dongre, PhD - Assistant Professor, Department of Biomedical Sciences, Department of Microbiology and Immunology Cornell University

Although immune checkpoint blockade therapy has generated dramatic responses in certain cancers, the response of breast tumors has been largely limited. By establishing novel, preclinical murine models of more-epithelial or more-mesenchymal breast tumors, we demonstrate that the cellular plasticity of breast cancer cells can itself be an important determinant of responsiveness to such therapy. Moreover, interrupting certain signalling channels specifically associated with mesenchymal cancer cells, can potentiate the effects of checkpoint inhibition leading to the elimination of more-mesenchymal breast tumors. Thus, our work highlights the prospect of using the polarization of carcinoma cells on the epithelial-mesenchymal spectrum as a surrogate marker for predicting responses to immune checkpoint blockade therapy.

 Jun 03, 2024 @ 12:00 p.m.

 Medical Center | Upper Auditorium (3-7619)

Host: Dept. of Microbiology & Immunology Seminar Series and Scott Gerber, PhD

Alex Pomakov, MD - Fellow, Univ. of Rochester Infectious Diseases Division

Meeting ID: 912 6958 5749

Passcode: 258684

 May 14, 2024 @ 11:45 a.m.

Jennifer Nayak, MD - Associate Professor, Department of Pediatrics, Infectious Diseases

 Apr 26, 2024 @ 9:00 a.m.

 Kornberg Medical Research Building | 3-9624

Felix Yarovinsky, MD - Professor, Department of Microbiology and Immunology, Center for Vaccine Biology and Immunology

 Apr 19, 2024 @ 9:00 a.m.

 Kornberg Medical Research Building | 3-9624

Joon Seok Park, Ph.D. - Instructor in Immunology, Harvard University

It has become clear that commensal microbes play important roles in maintaining immune homeostasis while responding robustly to foreign insults. A fascinating illustration of this process is the impact of gut microbes on the body’s immune defense against tumors located beyond the intestinal tract. My recent research revealed a novel underlying immune mechanism by which gut microbes promote anti-tumor immunity and opened novel research avenues for the exploration of cancer therapies. However, it remains enigmatic how gut-confined microbes can impact immune responses to distal tumors. Additionally, the precise context in which the gut microbe-mediated immune modulation become crucial in governing systemic immunity is poorly understood. My laboratory will determine 1) the immunomodulatory mechanisms mediated by commensal microbes in cancer and chronic viral infection 2) the roles of microbial lipids in innate signaling in the tumor microenvironment (TME) and 3) the mechanisms of crosstalk between the TME and gut microbiota. My research program will clarify the promise and limitations of cancer immunotherapy using gut microbiota and address why some cancers depend on gut microbiota and others do not. In addition, this work will tackle how specific gut microbes modulate systemic antiviral immunity leveraging our extensive information obtained from tumor studies, providing a unique direction to find the underlying mechanisms. This will guide the development of novel cancer immunotherapies and new approaches to improve vaccines.

 Apr 18, 2024 @ 4:00 p.m.

 Kornberg Medical Research Building | 3.9624

Paul Bohjanen, MD, PhD - Professor, Department of Medicine, Infectious Diseases

 Apr 12, 2024 @ 9:00 a.m.

 Kornberg Medical Research Building | 3-9624

Shawn Murphy, PhD - Associate Professor, Departments of Obstetrics & Gynecology and Microbiology & Immunology

 Apr 05, 2024 @ 9:00 a.m.

 Kornberg Medical Research Building | 3-9624

Yunlong Zhao, PhD - Assistant Project Scientist, School of Biological Sciences, University of California San Diego

Cancer immunotherapy is revolutionizing the way we fight disease, but many patients don't reap its full benefits. My research focuses on understanding how immune cells called T cells communicate with cancer cells and other immune cells. Typically, studies have focused on how receptor signals pass directly between cells. However, I also study how signals are exchanged in the same cell. These "internal conversations" can powerfully shape how T cells fight tumors. My work has shown that they can make T cells more effective against cancer. By carefully mapping how T cells talk to themselves, especially in cutting-edge therapies like adoptive cell therapy, I aim to uncover hidden targets for improvement. This knowledge could usher in a new era of immunotherapy where these incredible treatments work for even more patients.

 Mar 28, 2024 @ 4:00 p.m.

 Kornberg Medical Research Building | 3.9624

Clive Zent, MD - Professor, Department of Medicine, Hematology/Oncology

 Mar 22, 2024 @ 9:00 a.m.

 Kornberg Medical Research Building | 3-9624

Kristin Scheible, MD - Associate Professor, Department of Pediatrics, Neonatology & Microbiology and Immunology

 Mar 15, 2024 @ 9:00 a.m.

 Kornberg Medical Research Building | 3-9624

Kirsi Jarvinen-Seppo, MD, PhD - Professor, Department of Pediatrics, Pediatric Allergy/Immunology

 Mar 08, 2024 @ 9:00 a.m.

 Kornberg Medical Research Building | 3-9624

Joshua Anzinger, PhD - Senior Lecturer, Department of Microbiology
The University of the West Indies
Head of Virology, Consultant Virologist and
Director of Jamaica Affiliate Global Virus Network

Viral epidemics have become increasingly common worldwide. In Jamaica, viral epidemics have occurred every 2-3 years over the past decade, all on the backdrop of existing retrovirus epidemics. This seminar will provide a research-driven overview of recent viral epidemics in Jamaica and describe the capacity building approach to facilitate more effective research responses to future viral epidemics.

 Feb 29, 2024 @ 1:15 p.m.

 Medical Center | Lower Adolph Aud. (1-7619)

Host: Jacques Robert, PhD

Minsoo Kim, PhD - Professor, Department of Microbiology and Immunology, Center for Vaccine Biology and Immunology

 Feb 23, 2024 @ 9:00 a.m.

 Kornberg Medical Research Building | 3-9624

Brian Altman, PhD - Assistant Professor, Department of Biomedical Genetics

 Feb 16, 2024 @ 9:00 a.m.

 Kornberg Medical Research Building | 3-9624

Craig Morrell, DVM, PhD - Professor, Department of Medicine, Aab Cardiovascular Research Institute

 Feb 09, 2024 @ 9:00 a.m.

 Kornberg Medical Research Building | 3-9624

Ruchira Singh, PhD - Associate Professor, Dean's Proffesor of Ophthalmology, Biomedical Genetics, Center for Visual Science, and member of UR Batten Center

 Jan 31, 2024 @ 4:00 p.m.

 Kornberg Medical Research Building | G.11211 (CVRI Conf. Rm)

Host: Aab Cardiovascular Research Institute (CVRI) University of Rochester CVRI Seminar Series

Jacques Robert, PhD - Chair, Microbiology & Immunology

 Jan 26, 2024 @ 9:00 a.m.

 Kornberg Medical Research Building | 3-9624

Angela Branche, MD - Associate Professor, Department of Medicine, Infectious Diseases

 Jan 19, 2024 @ 9:00 a.m.

 Kornberg Medical Research Building | 3-9624