Year entered: 2020
Degrees received: Michigan State University
Research: My main focus is the vaginal microbiome and how it contributes to female reproductive tract health. A notable feature of female reproductive health is the vaginal microbiome; a seemingly simple community with very complex associations to health and disease. Recent studies surveying the vaginal microbiome of reproductive-age women have found the communities cluster into five groups, termed Community State Types (CST). The prevalence of each CST varies between different ethnic groups and biogeographical locations. On average, the vaginal communities in Black and Hispanic women are more diverse and harbor more anaerobic bacterial species, typically CST IV. Reasons for these differences are unknown, though maybe be due to lifestyle differences or other host factors. Further, women with a CST IV community are at increased risk of developing chronic BV, contracting HIV, and other pregnancy and reproductive health maladies. My goal is to contribute to efforts in identifying reasons for these differences and varied risk factors and developing treatment options.
Sabrina Arif (suh-BREE-nuh ARE-eef), (she/her)
Thesis Advisor: Ran Blekhman
Year entered: 2020
Degrees received: University of Colorado, Boulder
Research: The gut microbiome has a remarkable and varied influence on host health among the spectrum of human populations. Intestinal microbiomes of industrialized populations are compositionally different and less diverse than their rural counterparts and are associated with immune misregulation, driving gastrointestinal diseases such as ulcerative colitis, Crohn's disease, and colorectal cancer. However, because microbiome studies mostly identify correlations, it is not known if variation in the microbiome impacts host physiology, and through what mechanisms. Recent work demonstrates that microbiome exposure induces transcriptional changes in the mouse colon, suggesting an interplay among microbiota and interfacing host epithelial cells. In partnership with the laboratory of Francesca Luca, our group recently developed a novel in vitro co-culture system utilizing a human epithelial colonocyte cell line and live gut microbiomes and are currently developing an ex vivo system based on intestinal organoids. In 2019, application of the in vitro model demonstrated that interindividual microbiome variations illicit changes in host gene expression and chromatin accessibility that were driven by the abundance of specific taxa. Leveraging stool samples collected in collaboration with the Global Microbiome Conservancy, my PhD work will build upon these findings using the live microbiomes of industrialized and non industrialized populations. For this project, I will quantify the effect of interpopulation microbiome variation on host gene expression and understand its impact on host health. It is my aim to frontier the effort to provide a causal explanation to the established associations among human microbiomes and industrialization.
Thesis Advisor: Jeff Miller
Year entered: 2016
Degrees received: B.S., University of Minnesota, Twin Cities, 2014
MSc, Heidelberg University, Heidelberg, Germany 2016
Honors and awards:
$1000 award to attend NSF workshop on Crowdsourcing Innovation
My projects focus on developing Natural Killer (NK) cell-based cancer immunotherapy. To target cancer cells using Natural Killer (NK) cells, our lab developed a tri-specific killer engager (TriKE) molecule containing an anti-CD16 heavy chain antibody that activates NK cells, an IL-15 molecule that drives NK cell priming, expansion and survival, and an anti-CLEC12A single chain variable fragment (scFv) that engages cancer targets. CLEC12A is a cancer stem cell marker present on myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML) cells. This TriKE has great translational significance against cancers whose survival rates have not changes over the last ten years.
I am also interested in factors that impact NK cell function in the solid tumor microenvironment. A second project focuses on understanding how hypoxia impacts NK cells phenotype, function and metabolism under hypoxic condtions with the overall goal of improving anti-tumor immunity in solid tumor microenvironments.
Katherine (Maude) Ashby
Degrees received: University of Missouri
The T cell repertoire is shaped during thymocyte development in order to generate a mature T cell population with the ability to recognize diverse pathogens while minimizing the potential for autoimmunity. Following positive selection, interactions with self-antigens on antigen presenting cells can promote the clonal deletion or maturation of conventional or regulatory T cells. In this way, T cells can be removed from the repertoire or driven toward inert/regulatory lineages if they harbor reactivity to self-antigens encountered in the thymus. Thus, the nature of self-peptides presented by thymic antigen presenting cells has the potential to drastically affect mature T cell responses in the periphery. The transcriptional regulator AIRE promotes the thymic expression of a subset of self-antigens whose expression is otherwise restricted to specific tissues. As a result, AIRE expressing thymic APC promote tolerance to these tissue specific antigens. We are interested in other signals that may be critical in promoting the expression of distinct subsets of self-antigens in the thymus. Specifically, recent publications have pointed to the presence of inflammatory signals in the thymus at steady state (in the absence of infection,) which might have marked effects on antigen processing and presentation. We will investigate whether inflammation-induced self-antigens are presented to developing thymocytes, and how the presence of such antigens might affect T cell development and ultimately the functionality of the mature T cell repertoire. In some cases, these inflammatory signals are age dependent, peaking early in life and tapering with age. Thus, we also aim to understand the mechanisms regulating these signals in the thymus.
Sara Bolivar Wagers
View Sara's MD/PhD student profile here.
Thesis Advisor: Jeff Gralnick
Year entered: 2015
Bf.S., North Carolina State University, Raleigh, NCHonors and Awards:
- Viksnins, Harris & Padys MICaB Award, 2015
- BTI Travel Grant, 2016
- MPGI Travel Grant, 2016
Electricity is life. Cells use electrons in order to generate energy for the cell, but those electrons must go somewhere once they have been used because they cannot be destroyed. Humans breathe oxygen to accept electrons, but microorganisms have the ability to use a vast diversity of other compounds to accept electrons. One specialized strategy is to breathe metals such as Fe(III) and Mn(IV) as electron acceptors; however, Fe and Mn minerals are insoluble in most conditions. Microorganisms that utilize this metabolic strategy move electrons outside of the cell to the electron acceptor via extracellular electron transport. Shewanella and Geobacter are model systems for studying metal reduction, and we now know a general mechanism for extracellular electron transport in these microorganisms. There are numerous reports in the literature of microorganisms with the ability to breathe metals from all over the microbial tree of life. Microbes from extreme temperatures, pH, and salinity have all been described to perform metal reduction; however, many of these reports have not been investigated further with biochemical or genetic descriptions of how extracellular electron transfer is occurring. My PhD project is to discover and characterize novel pathways for extracellular electron transport in bacteria other than the model systems, Shewanella and Geobacter. Thus far I have characterized the mechanisms for extracellular electron transport in Aeromonas hydrophila, a cousin to Shewanella. Aeromonas spp. use aspects similar to Shewanella but also have unique components.
Degrees received: University of Illinois at Urbana-Champaign
Research: The emergence of antifungal drug resistance presents a global threat to human health. Candida albicans, the most prevalent opportunistic fungal pathogen, is of particular concern given its ability to rapidly acquire drug resistance. As a diploid species, it is an ideal system for studying genome dynamics during the acquisition of drug resistance. For example, loss of heterozygosity can result in fitness advantages in response to environmental stress. Known mechanisms of drug resistance include: 1) mutation or overexpression of the drug target; and 2) overexpression of the genes encoding drug efflux pumps. Importantly, Candida species can achieve this overexpression via large scale chromosomal rearrangements and copy number amplificiations. Such recombination events include but are not limited to aneuploidy, polyploidy, and isochromosome formations. Furthermore, many of these rearrangements confer antifungal drug resistance without a notable cost to fitness in the absence of drug. While these changes are known to occur, little is known about the rates, dynamics, and drivers of these evolutionary events. In order to better combat drug resistance, we need to identify when these changes occur and how they are selected for in a given microbial population. My work is largely focused on studying these evolutionary events via in vitro and in vivo evoltionary techniques as well as whole-genome sequencing to details these changes in a temporal fashion. Furthermore, I aim to identify how these rates, dynamics, and drivers of recombination contribute to antifungal drug resistance to mitigate future caseloads.
Degrees received: B.S., University of Minnesota, Minneapolis, MN, 2009
In the United States, one in seven men will be diagnosed with prostate cancer. Prostate cancer is an androgen-dependent disease, and androgen function is controlled by the androgen receptor (AR), a hormone activated transcription factor. Treatments targeting AR are highly effective at inhibiting disease progression. However, therapeutic resistance and emergence of castration resistant prostate cancer is responsible for virtually all prostate cancer mortality. Constitutively active AR splice variants have been implicated as drivers of castration resistant prostate cancer. AR variants consist of the unstructured AR NH2-terminal domain (NTD) and the AR DNA binding domain, but lack the ligand binding domain (LBD), which is targeted by current therapies. While our understanding of proteins that regulate the AR LBD is well developed, there is less known about the regulation of the NTD. This represents a significant gap in knowledge given that the AR NTD is the transcriptional “engine” of the AR and AR variants. To address this, the Dehm Lab used a new technique called RIME (rapid immunoprecipitation mass spectrometry of endogenous proteins) with a pair of isogenic prostate cancer cell lines that express either full-length AR or variant AR. This approach identified a cohort of proteins that interact with and are likely to regulate activity of the AR NTD. The identification of unknown AR regulators signifies a high potential for discovery related to AR function in castration resistant prostate cancer. Using molecular methods and bioinformatics tools, the objective of my research is to identify and characterize unknown AR regulators and their potential roles in prostate cancer development and progression.
Daniel M. and S.M. Dehm. 2017. Lessons from tissue compartment-specific analysis of androgen receptor alterations in prostate cancer. J Steroid Biochem Mol Biol. 166, 28-37.
View Natalie's MD/PhD student profile here.
Jenna (Johnson) Dick
View Jenna's MD/PhD student profile here.
View Minna's MD/PhD student profile here.
Degrees received: Rensselaer Polytechnic Institute
Phillip will be investigating the use of induced pluripotent stem cells (iPSC) in generating induced regulatory T cells (Tregs) as a cellular therapy for Graft Versus Host Disease. This process involves genetically modifying iPSC to increase their stability and propensity to differentiate into functioning Tregs and verifying the generated Tregs using genomic, proteomic, metabolomic and functional
View Alexander's MD/PhD student profile here.
Thesis Advisor: Kaylee Schwertfeger
Year entered: 2019
Degrees received: University of Minnesota, Twin Cities
The lymphatic vessel endothelial receptor (Lyve-1) is most well known as marker for lymphatic vessels. The Schwertfeger lab has now identified a population of macrophages in breast tumors that express Lyve-1. The role of Lyve-1+ macrophages in breast cancer is unknown; however, Lyve-1 is anti-tumorigenic in melanoma. I am seeking to understand the role of Lyve-1+ macrophages in breast cancer using mouse models and in vitro modeling experiments.
Degrees received: Ithaca College
Horizontal gene transfer is a near ubiquitous way for Bacteria and Archaea to acquire new genetic information. One mechanism of horizontal gene transfer is natural transformation, or the uptake/incorporation of DNA from the environment into the genome. In Bacteria, DNA uptake is often facilitated by extracellular appendages binding DNA to localize it within the cell. In Archaea, no mechanism of natural transformation has been previously identified. To date, our lab has identified two diverse Archaea that are capable of natural transformation and have shown that their ability to uptake DNA is dependent on type IV pili filaments. Overall, we seek to elucidate the remaining components of the DNA uptake pathway as well as investigate how conserved this mechanism is across the Archaeal domain.
View Noah's MD/PhD student profile here.
Thesis Advisor: Tyler Bold
Year entered: 2019
Degrees received: Purdue University
Explore the immune response to Mycobacterium tuberculosis infection focusing on adaptive immunity and T cells. Utilize mouse models and techniques including flow cytometry, flow-based cell sorting, RNA-seq, and adoptive transfer.
Year entered: 2019
Degrees received: University of Wisconsin, Stout
Cerebral malaria is a major disease affecting human health, resulting from extensive neuroinflammation during Plasmodium infections. The primary drivers of immunopathology during severe malaria are CD8 T cells. These cells traffic to the brain and disrupt the blood brain barrier, leading to extensive edema. Current malaria treatments focus on limiting parasite dynamics, but there are few therapies that modulate the immune system in this disease. One therapeutic approach involves stimulating the immune system to take on a more immunosuppressive and protective phenotype. Recent research has defined a role for natural killer cells to dampen the immune response. Our lab seeks to define mechanisms in which natural killer cells protect the host by limiting overt T cell responses during infection. These discoveries can be used to develop new treatments that target immunopathology during infection and autoimmune disease.
Degrees received: University of California, Davis
The Soudan Underground Mine in the Vermillion Range in northern Minnesota provides a unique opportunity to study the deep terrestrial biosphere that has been relatively unaffected by photosynthetic activities. The lowest level of the Soudan Underground Mine, which reach a depth of 713 meters, has access to 2.7-billion-year-old banded iron deposits with brine waters that are metal-rich, anoxic, and devoid of detectable organic carbon. Studying how microbes survive in the mine could help to understand the adaptations required to make a living in such unique conditions and how the microbial community, in turn, affects the geochemistry of the mine. The goal of my research is to enrich, isolate, and identify the microorganism that are playing a role in the metabolic cycling in the mine. Additionally, I will be studying the cytochrome-carrying prophage region of the Deltaproteobacterium Desulfuromonas soudanensis strain WTL, that was previously enriched from electrodes in the mine, to identify the role of horizontal gene transfer on the proliferation of cytochrome diversity in metal-reducing bacteria.
Degrees received: University of Wisconsin Milwaukee
Research: The epiphytic bacterium Methylorubrum extroquens is able to grow on reduced one carbon compounds, such as methanol. Doing so, however, presents a metabolic paradox. Methanol, and other one carbon compounds, are metabolized via a high flux oxidative pathway that produces formaldehyde as an obligate intermediate meaning formaldehyde is both a central metabolite and a potent stressor. Consequently, methylotrophs experience, and cope with, high intracellular concentrations of formaldehyde. My PhD research seeks to combine modern genetic techniques and classical bacteriological methodologies to focus on understanding and characterizing the regulatory mechanisms that allow M. extorquens to mount a formaldehyde specific stress response and maintain cellular homeostasis despite the presence of elevated formaldehyde.
Degrees received: B.S., Montana State University, Bozeman, MT, 2015
My research is focused on understanding the genetics and prevalence of fungal pathogens. Cryptococcus neoformans is an opportunistic pathogen found worldwide. C. neoformans causes cryptococcal meningitis in HIV/AIDS patients, accounting for half a million deaths annually in Africa. Previous members of the Nielsen lab found a correlation between cryptococcal MLST type and patient outcome. Whole genome sequencing identified SNP differences in alleles between representative strains of these MLST subgroups. My research is focused on determining which of these SNP differences are important in cryptococcal virulence. I will use these findings to build a PCR based system to screen for these alleles in a larger clinical strain set. This data will allow us to predict patient outcome based on the allele variant.
Blastomyces dermatitidis is a primary fungal pathogen endemic to the Great Lakes region. B. dermatitidis is rarely isolated from the environment, and its ecological niche is not well understood. Due to the difficulties of cultivating B. dermatitidis from the environment, we are using a culture independent method of detection to track B. dermatitidis prevalence in Minnesota. Utilizing a combination of non-random samples taken from areas assumed to be in risk areas for B. dermatitidis , and random samples collected in three geographical regions of Minnesota, I will identify B. dermatitidis risk areas. I plan to use this data to determine if there is ecological similarity between B. dermatitidis high risk areas to increase our understanding of this fungus' ecological niche and environmental presence.
View Robin's MD/PhD student profile here.
Degrees received: B.A., University of Texas, Austin, 2006
B.S., University of Texas, Austin, 2006
Shewanella oneidensis is an iron respiring gamma-proteobacterium with unique electrical properties. It appears to have the ability to migrate toward areas of high redox potential by sensing redox gradients of the flavin molecules that it excretes. Dubbed electrochemotaxis, this novel form of taxis is poorly understood. The goal of my research is to identify the mechanism and genetic underpinnings of flavin electrochemotaxis, which may shed light on how some organisms are able to localize to insoluble substrates necessary for their survival.
Degrees received: Colorado State University
Cystic Fibrosis is a genetic disorder that affects ~70,000 people worldwide. This disease is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) and is characterized by the accumulation of thick, sticky mucus in the lower respiratory airways. This accumulation allows for chronic microbial colonization and infection of the lungs leading to a decreased lifespan. By studying this microbial colonization and its dynamic interplay within itself as well as with the host, I aim to elucidate what role bacteria are playing as major pathogens in this disease as well as the role of the host immune response.
Degrees received: University of Michigan, Ann Arbor
Research: My research is focused on investigating innate immunity to Mycobacterium tuberculosis (Mtb) infection focusing on myeloid cell populations. Utilizing mouse models, single cell RNA sequencing, and fluorescent/barcode labeled Mtb strains, I aim to elucidate different cell phenotypes between infected and bystander populations. I also have interests in investigating the mycobacterial genetic requirements for surviving the macrophage response.
View Fathima's MD/PhD student profile here.
Degrees received: University-Michigan Ann Arbor
The goal of my research is to investigate the inhibitory effects of cellular activation on NK cell anti-cancer immunity, how this dysfunction can be rescued, and the cellular mechanisms that govern these processes. In particular, I am interested in the metabolic changes associated with NK cell exhaustion and how the tumor microenvironment influences this phenotype.
Degrees received: B.S., Minnesota State University, Mankato, MN, 2010 and M.S., University of Northern Iowa, Cedar Falls, IA , 2014
The APOBEC3 family of cytidine deaminases are anti-viral restriction factors that exhibit activity against a wide variety of reverse-transcribing retroviruses and retroelements by converting cytosines-to-uracils in single stranded DNA. While APOBEC3 enzymes are a critical component of the innate immune system, recent studies indicate that APOBEC3B, which is upregulated in several different cancer types, is a major source of mutation in primary and metastatic tumors. Tumors that express high levels of APOBEC3B generally have enhanced mutational burdens. I am investigating the possible relationship between APOBEC3B mutation, neoepitope generation, and responses to immunotherapy.
Degrees received: B.A., St. Catherine University, St. Paul, MN 2014
Honors and Awards:
- Viksnins, Harris & Padys MICaB Award, 2016
- NSF Graduate Research Fellowship, 2017 - present
Malignant Peripheral Nerve Sheath Tumors (MPNST’s) are aggressive soft tissue sarcomas often associated with neurofibromatosis type 1 (NF1). NF1 is one of the most common genetic disorders arising due to a mutation in the NF1 gene. NF1 encodes neurofibromin, a Ras GTPase-activating protein. Functional neurofibromin is crucial for proper Ras-signaling homeostasis, while mutant variants are often unable to effectively modulate Ras signaling. Hyperactive Ras signaling activates both the MAPK and PI3K pathways, leading to excessive cell growth and proliferation. In Schwann cells in the PNS, this excessive cellular growth and proliferation gives rise to benign tumors known as neurofibromas. These tumors, although initially benign, have an increased propensity to progress to MPNST. Precise factors governing this progression are unknown. Our lab has identified a number of candidate factors that may be important in this malignant transformation. We are also targeting these factors as potential therapies for MPNST.
Stephen (Buck) O'Flanagan
Degrees received: Bethel University, MN
Tissue resident memory T cells (T RM ) patrol peripheral tissues without recirculating through blood or lymph and play a critical role in front-line protection from viral infections. Recently, the Masopust lab reported the existence of bona fide lymph node resident memory T cells (LN T RM ). Although LN T RM may constitute a significant proportion of memory T cells in human lymph nodes, their function is entirely unknown. My research aims to define the ontogeny, fate, and function of LN T RM . I will investigate the specific contributions of LN T RM to lymph node immunosurveillance, local viral clearance, and orchestration of memory immune responses.
View Elizabeth's MD/PhD student profile here.
Degrees received: B.S., University of Wisconsin, Stout-Menomonie, WI, 2013
My research is focused around the idea of anergy in CD4+ T cells. Anergy is a functional unresponsiveness that results from incomplete or altered activation signals. My goals are to find the peptides that are driving CD4+ T cells to become anergic, and characterize their role in infection and autoimmunity.
Degrees received: Florida International University
Research: Title: Molecular mechanisms of PARP inhibitor sensitivity in ovarian cancer
Ovarian cancer continues to be the most lethal gynecologic malignancy in the US, with High Grade Serous Ovarian Cancer (HGSOC) being the most common and most lethal subtype of cancer. Germline deleterious mutations in BRCA1 and BRCA2 are associated with carcinogenesis, are involved in contributing to homologous recombination dysfunction, and can be therapeutically exploited using PARP inhibitors. Despite the synthetic lethal action of PARP inhibitors on BRCA1/2 mutated cancers, drug resistance develops and the majority of patients relapse. In addition, the precise role of PARP inhibition on wild-type BRCA1/2 HGSOCs is unclear, warranting further study on the mechanism of action in ovarian cancers with different genomic backgrounds. The goal of my research is to study the molecular mechanisms of PARP inhibition in HGSOCs containing BRCA1/2 mutations and comparing these responses to wild-type BRCA1/2 ovarian cancers. By studying the differential responses that HGSOCs have on PARP inhibition at the level of the proteome, we can ascertain which type of HGSOCs would benefit most with PARP inhibition with minimal risk of relapse. Finally, studying changes in the proteome upon PARP inhibition will reveal other sets of genes besides BRCA1/2 that are involved in homologous recombination dysfunction.
Thesis Advisor: Ryan Langlois
Year entered: 2019
Degrees received: California State University, Long Beach
My thesis research focuses in two different areas: virus transmission and evolution, as well as viral immunology. The virus transmission and evolution project is aimed to understand the genetic diversity of circulating viruses in order to identify the process of spillover transmission. For my viral immunology project, I sought to identify the mechanisms that permit some lung epithelial cells to survive influenza infection in the presence of innate immune response.
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View Julia's MD/PhD student profile here.
Degrees received: University of Minnesota, Morris
Pancreatic ductal adenocarcinoma (PDA) is currently the third leading cause of cancer-related deaths in the U.S. PDA commonly presents with advanced unresectable disease. The robust desmoplastic microenvironment and compromised perfusion contribute to drug resistance. Immunotherapies have become a major success in the treatment of cancer but unlike other solid tumors, immune checkpoint blockade monotherapies have largely failed in PDA. Previous work by Dr. Stromnes and colleagues established that an adoptive cell therapy with T cells engineered to express T cell receptor specific to the overexpressed self/tumor antigen, mesothelin (TCR Msln ) is safe and prolongs survival in a genetically engineered PDA mouse model. Engineered TCR Msln T cells preferentially accumulate in PDA, induce tumor cell death, and alter the dense stromal microenvironment. However, over time, engineered T cells progressively become dysfunctional requiring serial T cell infusions for efficacy. Understanding the mechanisms underlying engineered T cell dysfunction and how we can circumvent this dysfunction is the focus of my research. I hypothesize that a combination of chronic TCR signaling and tumor microenvironment (TME) in pancreatic cancer interferes with engineered T cell anti-tumor activity. To begin to address this question, my studies will incorporate a novel mesothelin TCR knock-in mouse we recently created as tool to probe how to modify the TME and the T cell for more durable responses with cell-based therapies.
Degrees received: University of Wyoming
Research: I am working to understand the role of steroid hormone receptor signaling (estrogen receptor, ER, and the progesterone receptor, PR) in luminal (ER+) breast cancer (BC) that has acquired both endocrine resistance and endothelial to mesenchymal transition. Specifically, elucidating the signaling events that lead to expansion of a subpopulation of CD44high/CD24low cancer cells, circulating stem cell (CSC) like cells, within endocrine resistant BC. In previous models, ER is thought to be down regulated in endocrine resistance; yet PR, (which is induced by ER), exhibits increased transcriptional activity. To understand what is driving these signaling events leading to a CSC phenotype, I am creating new models of endocrine resistance in multiple cell lines and comparing the signaling components in 2D versus 3D tissue culture conditions. Additionally, these TC models will be expanded to mouse models for in vivo characterization. Learning more about the roles of ER and PR in driving the stem cell-like subpopulation within BC resistance will provide insight into mechanisms of cancer cell plasticity and possible reversal of endocrine resistance.
Thesis Advisor: Ingunn Stromnes
Year entered: 2019
Degrees received: Grinnell College
Tumor cell loss of MHC class I remains is a critical barrier to successful immunotherapy. The goal of my research is to understand immune evasion of pancreatic ductal adenocarcinoma (PDA) and identify immune cell populations that either promote tumorigenesis or are critical for the anti-tumor immune response in MHC class I loss variants. Specifically, using an orthotopic model of
PDA that expresses the click beetle neoantigen I will investigate how loss of MHC class I expression causes tumor escape and an unsuccessful immune response. Moreover, I hope to identify therapeutically targetable immune cells and pathways that can be leveraged to induce disease remission in MHC class I loss variants of PDA.
Degrees received: B.S., University of Minnesota, Twin Cities, Minneapolis, MN, 2008
Tissue-resident memory CD4+ and CD8+ T cells (TRM) have been identified in many tissues and organs of mice and humans. TRM reside in barrier (e.g., skin, gut, and lung) and non-barrier tissues (e.g., pancreas, kidney, liver, brain, and SLOs). TRM are the dominant T cell population involved in immunosurveillance of most organs and upon activation they are capable of in-situ proliferation, producing proinflammatory cytokines, recruiting circulating memory cells and B cells, as well as other functions. These abilities make TRM important players in monitoring and protecting the tissues they occupy from infection and cancer. Recently, there is an increasing awareness that they also likely promote unfavorable responses such as inflammatory diseases, transplant rejection, allergy, and autoimmune diseases that include inflammatory bowel disease, vitiligo, and multiple sclerosis. If TRM do have a prominent role in immunopathology, elimination of TRM in affected tissues may reduce levels of inflammation and close those tissues to routine immune surveillance, allowing for durable remission. My research project is focused on understanding how tissue-resident memory T-cell populations are generated and maintained in peripheral tissues and in developing depletion strategies explicitly targeted against tissue-resident memory T-cell populations. Depletion strategies can be tested in relevant autoimmune and allergic mouse models as well as transplant models in both clean and dirty mice, and will also help elucidate tissue-specific mechanisms of T cell recruitment, retention, and homeostasis.
Degrees received: B.A., University of Minnesota, Twin Cities, Minneapolis, MN, 2013
Regulatory T cells (Tregs) are critical for maintaining immune homeostasis and preventing autoimmunity. We have discovered a population of Tregs and Treg progenitor cells within the thymus that express a strong interferon (IFN) stimulated gene signature. The goal of my thesis research is to understand the development and function of these cells. We hypothesize that IFN signaling in the thymus induces the expression of ISGs in antigen presenting cells and that these serve as antigens for priming and differentiation of thymic Tregs. We believe that this population of Tregs are specialized for responding to and controlling IFN driven inflammation.
View Philip's MD/PhD student profile here.
Degrees received: University of California, San Diego
Checkpoint blockade using anti-PD1 and anti-CTLA4 has been successfully employed to treat various cancers such as melanoma, lung cancer and Hodgkin’s lymphoma. Most of these cancers have a high number of mutations are thus highly immunogenic. However, the efficacy of checkpoint blockade has been low in cancers with a low mutation burden. BCR-ABL + B cell Acute Lymphoblastic Leukemia (B-ALL) is one such type of cancer that occurs in children and adults. Although current treatment modalities are highly effective in children, the efficacy in adults is significantly lower. Previous work from our laboratory has demonstrated that T cells specific for the BCR-ABL fusion peptide are converted to Tregs during the course of leukemia and inhibit anti-tumor immunity. Vaccination with the BCR-ABL peptide, followed by heterologous priming with various viruses and checkpoint blockade improved survival in mice with B-ALL. My project aims at characterizing the immune cells that are necessary for a protective anti-leukemia immune response, and to develop strategies involving checkpoint blockade to induce the same. Specifically, we are interested in understanding the contribution of cytotoxic CD4 T cells and type-I interferon to the anti-leukemia immune response in-vivo.
Degrees received: B.S., University of Wisconsin, Madison, 2017
Cystic Fibrosis (CF) is a genetic condition resulting from the loss of function of the CFTR membrane proteins, and leading to the accumulation of viscous mucin in the airways that results in chronic inflammation and infection. Pseudomonas aeruginosa is a canonical airway pathogen frequently found in these chronic infections, and has demonstrated an inability to sustain its nutrient requirements on mucin as a sole carbon source. Rather, it requires the presence of mucin-degrading anaerobes to produce mucin degradation products for use as a nutrient source. This cross-feeding relationship has been shown to elicit the production of vital pathogenesis related virulence factors from Pseudomonas, such as pyocyanin. Interestingly, when Pseudomonas is grown on the mucin byproducts of anaerobes derived from clinical patient samples, virulence factor production varies greatly between patients. My work in the Hunter lab focuses on investigating the cause of this varied virulence factor expression, and exploring the broader picture of the role of pulmonary microbial community composition in Pseudomonas aeruginosa virulence in the cystic fibrosis airways.
View Kelsey's MD/PhD student profile here.