Student Profile

Madison Ahmad

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Email: ahmad217@umn.edu

Thesis Advisor: Nichole Klatt

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.

 

Katherine (Maude) Ashby

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Email: ashby037@umn.edu

Thesis Advisor: Kris Hogquist

Year entered: 2018

Degrees received: University of Missouri

Research: 

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.

 

Alison Barkhymer

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Email: Barkh007@umn.edu

Thesis Advisor: Ryan Langlois

Year entered: 2020

Degrees received: Minnesota State University, Moorhead

Research: 

Influenza is a virus that can infect many species, but in order to cross species barriers it has to overcome a number of obstacles. One of these obstacles is the host antiviral immunity. Interferon-stimulated genes (ISGs) are expressed in response to viral infection and make up a large component of the antiviral immune response. I am investigating the function of interferon-stimulated genes in the cross-species transmission barrier of influenza.

 

Carlo Castillo

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Email: casti083@umn.edu

Thesis Advisor: Ryan Hunter

Year entered: 2021

Degrees received: The Ohio State University

Research: 

Taylor Crooks

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Email: Crook142@umn.edu

Thesis Advisor: Anthony Baughn

Year entered: 2020

Degrees received: University of Illinois at Urbana-Champaign

Research:   The emergence of drug resistance in Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, presents a threat to both developed and impoverished countries around the world. My work is largely focused on characterizing antitubercular drug activity in Mtb, more specifically, pyrazinamide and pyrazinamide analogs. While pyrazinamide is an important first line therapeutic in tuberculosis treatment, its exact mechanism is unclear. My research employs various in vitro techniques to study changes of fitness in drugs using genetics-based approaches such as transposon mutagenesis and targeted knockouts. The goal of my research is to elucidate the molecular mechanisms of an effective, yet uncharacterized, pyrazinamide analog in the hopes of better understanding pyrazinamide/pyrazinamide analog activity in Mtb.

Eduardo Cruz

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Email: cruzh004@umn.edu

Advisor: Ingunn Stromnes

Year entered: 2021

Ungergraduate Institution: University of California Irvine

Research:

Natalie David

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View Natalie's MD/PhD student profile here.

Taylor DePauw

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Email: depa0049@umn.edu

Advisor: Steve Jameson

Year entered: 2021

Ungergraduate Institution: University of Wisconsin Stout

Research:

Jenna (Johnson) Dick

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View Jenna's MD/PhD student profile here.

Minna Ding

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View Minna's MD/PhD student profile here.

Phillip Dougherty

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Email: dough229@umn.edu

Thesis Advisor: Bruce Blazar

Year entered: 2018

Degrees received: Rensselaer Polytechnic Institute

Research: 

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
assays.

Alexis Elfstrum

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Email: elfst022@umn.edu

Thesis Advisor: Kaylee Schwertfeger

Year entered: 2019

Degrees received: University of Minnesota, Twin Cities

Research:

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.

Jordan Ernest

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Email: ernes021@umn.edu

Advisor: Mike Farrar

Year entered: 2021

Ungergraduate Institution: Pennsylvania State University

Research:

Dallas Fonseca

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Email: fonse039@umn.edu

Thesis Advisor: Kyle Costa

Year entered: 2018

Degrees received: Ithaca College

Research:

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.

Noah Gavil

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View Noah's MD/PhD student profile here.

Abby Gress

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Email: gress045@umn.edu

Thesis Advisor: Tyler Bold

Year entered: 2019

Degrees received: Purdue University

Research: 

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.

Jacob Hildebrand

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Email: hilde236@umn.edu

Thesis Advisor: Sara Hamilton Hart

Year entered: 2019

Degrees received: University of Wisconsin, Stout

Research:

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.

David Hsu

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Email: hsu00002@umn.edu

Thesis Advisor: Jeffrey Gralnick

Year entered: 2018

Degrees received: University of California, Davis

Research:

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.

Ri-Sheng (Rex) Huang

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Email: huan2380@umn.edu

Advisor: Branden Moriarity

Year entered: 2021

Undergraduate Institution: National Taiwan University

Research:

Robert Hullsiek

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Email: hulls015@umn.edu

Advisor: Bruce Walcheck

Year entered: 2021

Undergraduate Institution: University of Minnesota

Research:

Zak Hying

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Email: Hyin0002@umn.edu

Thesis Advisor: Jannell Bazurto

Year entered: 2020

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.

Julia Jackson

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Email: jack1850@umn.edu

Admisor: Dave Masopust

Year entered: 2021

Undergraduate Institution: Univ. of California Berkeley

Research:

Katrina Jackson

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Email: jack1324@umn.edu

Thesis Advisor: Kirsten Nielsen

Year entered: 2017

Degrees received: B.S., Montana State University, Bozeman, MT, 2015

Research:

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.

 

Sookyong Joo

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Email: joo00015@umn.edu

Advisor: Mike Farrar

Year entered: 2021

Undergraduate Institution: Macalester College

Research:

Sylvia Klein

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Email: klei0916@umn.edu

Advisor: Matt Aliota

Year entered: 2021

Undergraduate Institution: St. Mary's College

Research:

Ruth Lee

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Email: leex9181@umn.edu

Thesis Advisor: Jeffrey Gralnick

Year entered: 2017 

Degrees received: B.A., University of Texas, Austin, 2006
B.S., University of Texas, Austin, 2006 

Research:

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.

Anders Lindstedt

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View Anders' MD/PhD student profile here.

Nicole Marquez Reyes

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Email: mrque001@umn.edu

Advisor: Kathryn Fixen

Year entered: 2021

Undergraduate Institution: University of Puerto Rico, Cayey

Research: Rhodopseudomonas palustris is an anoxygenic phototroph that is metabolically versatile. Being able to switch between different modes of metabolism allows for its commercial and industrial application (ex. biodegradation of aromatic compounds from industrial waste; the production of H2 as a by-product of N2 fixation by the enzyme nitrogenase). Recently, a family of nitrogenase-like enzymes called Methylthio-alkane Reductases (Mar), has been a focus of study. In order to make methionine (an important amino acid), Mar enzymes utilize methyl-thio ethanol (MT-EtOH) as a sulfur source, and while it does this, it produces ethylene as a by-product. Ethylene is a volatile organic sulfur compound that has been described to have an effect in soil environments and climate. This compound is an important phytohormone, helping plants handle certain stresses such as pathogens. Other applications of ethylene are that the compound is a precursor to plastics. Additionally, ethylene in its oxidized form is a potent carcinogen. Some bacteria found in the soil or gut microbiome have at least one Mar enzyme, while R. palustris has multiple. The focus for my Ph.D. is to further characterize R. palustris’ Mar isozymes and how they contribute to ethylene production and sulfur-cycling, utilizing genetic and physiological approaches. Additionally, since R. palustris has multiple Mar enzymes, we want to further study and test the hypothesis of these different Mar variants potentially utilizing different metal cofactors similar to the nitrogenase enzymes.

Richard Martinez

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Email: mart5176@umn.edu

Thesis Advisor: Ryan Hunter

Year entered: 2018

Degrees received: Colorado State University

Research:

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.

Tailor Mathes

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Email: Mathe709@umn.edu

Thesis Advisor: Tyler Bold

Year entered: 2020

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.

Fathima Mohamed

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View Fathima's MD/PhD student profile here.

Jacob Myers

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Email: myers892@umn.edu

Thesis Advisor: Jeffrey Miller

Year entered: 2018

Degrees received: University-Michigan Ann Arbor

Research: 

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.

Jordan Naumann

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Email: jnaumann@umn.edu

Thesis Advisor: Reuben Harris

Year entered: 2017 

Degrees received: B.S., Minnesota State University, Mankato, MN, 2010 and M.S., University of Northern Iowa, Cedar Falls, IA , 2014

Research:

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.

 

Tristan Neal

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Email: neal0232@umn.edu

Advisor: Ryan Langlois

Year entered: 2021

Undergraduate Institution: Arizona State Univ. of Tempe

Research:

Julia Nikrad

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Email: nikr0006@umn.edu

Thesis Advisor: David Largaespada

Year entered: 2016

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

 

Research:

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

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Email: oflan004@umn.edu

Thesis Advisor: David Masopust

Year entered: 2019

Degrees received: Bethel University, MN

Reasearch:

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.

Elizabeth Okafor

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View Elizabeth's MD/PhD student profile here.

Kevin Osum

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Email: kcosum@umn.edu

Thesis Advisor: Marc Jenkins

Year entered: 2017 

Degrees received: B.S., University of Wisconsin, Stout-Menomonie, WI, 2013

Research:

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.

Michael Patterson

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View Michael's MD/PhD student profile here. 

Jesenia Perez

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Email: Perez888@umn.edu

Thesis Advisor: Stefani Thomas

Year entered: 2020

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.

Mary Piaskowski

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Email: piask003@umn.edu

Advisor: Roberta O'Connor

Year entered: 2021

Undergraduate Institution: Marshall University

Research: Apicomplexan parasites cause disease in both humans and domesticated animals with potentially devastating impacts. Treatments targeting such infections are lacking. Two examples being Toxoplasma gondii, which is capable of establishing an  untreatable latent infection in all warm-blooded animals, and Cryptosporidium parvum which is a common cause of childhood diarrhea worldwide, and the single drug used to treat it is inadequately effective. Naturally derived compounds have long been a source of antimicrobial drugs. Recent research has turned to searching  for antiparasitic compounds from marine animals. My goal is to study the effects of some of these marine derived bioactive compounds on the apicomplexan parasites Cryptosporidium parvum and Toxoplasma gondii. To do this, I am assessing efficacy against infection and identifying drug targets through molecular biology techniques.

Foster Powers

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Email: power657@umn.edu

Advisor: Tyler Bold

Year entered: 2021

Undergraduate Institution: University of Arizona

Research: 

I am exploring T cell specificity in the context of Mycobacterium tuberculosis infection.  This includes their interactions with antigen presenting cells and characterization of these T cells throughout the course of TB infection.  I will be using in vivo (murine) methods as well as analysis techniques such as single cell RNA/TCR sequencing and PIC-sequencing to in an effort to understand how antigen specificity may contribute to or direct T cell phenotype and activation.

Dira Putri

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Email: dputri@umn.edu

Thesis Advisor: Ryan Langlois

Year entered: 2019

Degrees received: California State University, Long Beach

Research: 

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.

Meagan Rollins

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Email: rolli080@umn.edu

Thesis Advisor: Ingunn Stromnes

Year entered: 2018

Degrees received: University of Minnesota, Morris

Research: 

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.

Tyler Rollman

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Email: Rollm004@umn.edu

Thesis Advisor: Craig Bierle

Year entered: 2020

Degrees received: Creighton University

Research: 

Susan Schmidt

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Email: Schm5475@umn.edu

Thesis Advisor: Carol Lange

Year entered: 2020

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. 

Zoe Schmiechen

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Email: schm5267@umn.edu

Thesis Advisor: Ingunn Stromnes

Year entered: 2019

Degrees received: Grinnell College

Research: 

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.

Milcah Scott

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Email: scot0340@umn.edu

Thesis Advisor: David Masopust

Year entered: 2017 

Degrees received: B.S., University of Minnesota, Twin Cities, Minneapolis, MN, 2008

Research:

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.

Lucy Sjaastad

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Email: sjaas005@umn.edu

Thesis Advisor: Michael Farrar

Year entered: 2017 

Degrees received: B.A., University of Minnesota, Twin Cities, Minneapolis, MN, 2013

Research:

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.

Olivia Smith

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View Olivia's MD/PhD profile here.

Claire Thefaine

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Email: thefa002@umn.edu

Thesis Advisor: Sara Hamilton Hart

Year entered: 2020

Degrees received: University of North Carolina, Chapel Hill

Research: 

Memory CD8 T cells provide us with long-term protection against reinfection by intracellular pathogens. The CD8 T cells memory pool is heterogenous; our group has recently defined a rare circulating subset known as long-lived effector cells (LLECs) which are characterized by their expression of KLRG1 and superior control of LM. Months after infection in SPF mice, the LLEC population wanes in comparison to other subsets. However, this does not seem to be the case in “dirty mice,” which have higher systemic pro-inflammatory cytokine levels. My work centers around the hypothesis that LLECs are uniquely able to utilize pro-inflammatory cytokines such as IL-18 for their maintenance.

Jose Valentin Lopez

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View Jose's MD/PhD profile here.

Hrishi Venkatesh

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Email: venka201@umn.edu

Thesis Advisor: Michael Farrar

Year entered: 2018

Degrees received: University of California, San Diego

Research: 

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.

Alex Villarreal

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Email: villa467@umn.edu

Thesis Advisor: Ryan Hunter

Year entered: 2017 

Degrees received: B.S., University of Wisconsin, Madison, 2017

Research:

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.

Sarah Wall

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View Sarah's MD/PhD student profile here.