Immunobiology
Immunology Graduate Program

Immunology Graduate Program

The Immunology Graduate Program (ImmGP) is an inter-departmental program within the University of Cincinnati (UC) and Cincinnati Children’s that offers PhD and MS degrees in Immunology. The program is managed by Director Dr. David Hildeman, and a steering committee composed of members of several departments/divisions at Cincinnati Children's and UC. Dr. Jonathan Katz is the Director of the MS program. Notably, the ImmGP is partially supported through an NIH T32 training grant, “Pathogenesis and therapeutic targeting of Immune disorders”.

The ImmGP provides broadly based instruction in immunology, along with rigorous research training that emphasizes cutting-edge approaches to understanding the function of the immune system in health and disease. To this end, the program currently has 50 faculty members from 6 departments and 15 divisions within UC College of Medicine and Cincinnati Children's. We currently have a total of 38 outstanding students (32 PhD students and 6 MS students) from around the country and abroad. This academic year we celebrated the graduation of 8 PhD students. Graduates are highlighted on the below student lists in bold. Our students have distinguished themselves this year by receiving several travel and research awards.

The program is supported financially by a variety of sources. This year, tuition support was provided through University Graduate Scholarships awarded by UC. Student stipends were supported through a variety of sources including funds from an NIH T32 training grant, UC, NIH NRSA grants, external grants to their advisors, and funds from Cincinnati Children's Research Foundation.

In spring 2013, the ImmGP established an International Research Training Group (IRTG) with the University of Lübeck/Research Center Borstel in Lübeck, Germany. Largely due to the dedication and stellar research programs of the faculty here at Cincinnati Children's and at the University of Lübeck/Research Center Borstel, this international grant was renewed after an on-site review in Lubeck in 2017.

The research focus of the IRTG is:

  1. Humoral and Cellular Pathways of Allergic Inflammation
  2. Immuno-regulation of infection-driven inflammation

ImmGP students interested in research projects encompassed by these areas may have the opportunity to study and perform research in the beautiful city of Lübeck in north-central Germany for a 3-6 month period.

Doctoral Students

Students in bold graduated with their PhD.

Start Year Student Name Lab
2013 Paige Bolcas Hershey
2013 Kaitlin Carroll Katz
2013 Jonathan Fletcher Ratner
2013 Courtney Jackson Chougnet
2013 Andrew Patterson Hoebe
2014 Katelyn Melgar Starczynowski
2014 Anna Sliz Hoebe
2014 Kathryn Sullivan Herr
2015 Calvin Chan Divanovic
2015 Sydney Felker Mailk
2015 Seth Reighard Waggoner
2015 Sharmila Shanmuganad Hildeman
2015 Amnah Yamani Hogan
2016 Corinne Foley Hwa
2016 Tammy Hunter Herr
2016 Tzu-Yu Shao
2016 Alyssa Thomas Janssen
2016 Jazib Uddin Hogan
2016 Nicholas Weaver Spearman
2016 Adrienne Wilburn Divanovi
2017 Ayad Ali Waggoner
2017 Tareian Cazares Miraldi
2017 Melanie McKell Qualls
2017 Oscar Negron Flick
2017 Jarren Oates Divanovi
2017 Benjamin Weinhaus Lucas
2017 Xiangfei Xie Rotating
2018 Madeline Bonfield Deshmukh
2018 Rachel Cantrell Palumbo
2018 Audrey Crowther Salomonis
2018 Rebecca Crowther Qualls
2018 Hannah Meibers Pasare
2018 Anastasiya Slaughter Lucas
2018 Annie Song Grimes

MS Students

Start Year Student Name Lab
2018 David Dylan Filippi
2018 Eric Eymard Barski
2018 Wen Gao Hwa
2018 Huaman Moises
2018 Travis Isaacs Chougnet
2018 Jaidaa Ismail Herr
2018 Michelle Robillard Qualls

Student Awards

Ayad Ali 2017

  • AAI Young Investigator Award – Autumn Immunology Conference (AAI) 11/2018
  • Honorable Mention - Graduate Student Research Forum University of Cincinnati 10/2018
  • AAI Trainee Abstract Award – Annual American Association of Immunologists Meeting (AAI) 3/2019

Tareian Cazares 2017

  • Decart SummerSchool URM scholarship, Data Science for Healthcare, University of Utah, Flights, Housing and Tuition

Tammy Gonzalez 2016

  • American Academy of Allergy, Asthma, and Immunology PhD Travel Award
  • Asthma and Allergic Diseases Cooperative Research Centers (AADCRC) Trainee Travel Award
    • AAAAI Chrysalis Project Award - April 2018: This three-day program introduces you to the breadth of Allergy / immunology. Includes a travel award and membership to AAAAI. Presents A/I career options and participants are paired with Fellow-in-Training (FIT) mentors.
    • ASM Graduate Research Fellowship - June 2018

Melanie McKell 2017

  • Graduate Student Research Forum Honorable Mention, University of Cincinnati, College of Medicine Fall 2018

Seth Reighard 2015

  • First Place: U. of Cincinnati 39th Annual Graduate Student Research Forum (2018)
  • AAI Young Investigator Award (2018 Cincinnati Children's Hospital Medical Center Immunology Retreat)

Tzu-yu Shao 2016

  • The AAI Young Investigator Award, 47th Autumn Immunology Conference 11/2018
  • SLB Trainee Award, Annul Immunology Retreat 10/2018
  • The AAI Young Investigator Award, Annual Immunology Retreat 10/2018
  • Albert J. Ryan Fellowship

Anastasiya Slaughter 2019

  • Young Investigator Award Best Talk, American Association of Immunologists- October 2018

Anna Sliz 2014

  • Trainee Abstract Award, Annual American Association of Immunology Conference 2019

Publications

Paige Bolcas 2013

  • Bolcas PE, Brandt EB, Zhang Z, Biagini Myers JM, Ruff BP, Khurana Hershey GK. Vitamin D supplementation attenuates asthma development following traffic-related particulate matter exposure. J Allergy Clin Immunol. 2018 Jun 21. pii: S0091-6749(18)30898-4. PMID: 29936100
  • Patterson AR, Bolcas P, Lampe K, Cantrell R, Ruff B, Lewkowich I, Hogan SP, Janssen EM, Bleesing J, Khurana Hershey GK, Hoebe K. Loss of GTPase of immunity-associated protein 5 (Gimap5) promotes pathogenic CD4(+) T-cell development and allergic airway disease. J Allergy Clin Immunol. 2019 Jan;143(1):245-257.e6. doi: 10.1016/j.jaci.2018.10.018. Epub 2018 Oct 25. PMID:30616774|PMCID:PMC6327968

Calvin Chan 2015

  • Chan CC, Damen MSMA, Alarcon PC, Sanchez-Gurmaches J, Divanovic S. Inflammation and Immunity: From an Adipocyte's Perspective. J Interferon Cytokine Res. 2019 Mar 28. doi: 10.1089/jir.2019.0014. [Epub ahead of print]. PMID:30920343
  • Zhang C, Seo J, Murakami K, Salem ESB, Bernhard E, Borra VJ, Choi K, Yuan CL, Chan CC, Chen X, Huang T, Weirauch MT, Divanovic S, Qi NR, Thomas HE, Mercer CA, Siomi H, Nakamura T. Hepatic Ago2-mediated RNA silencing controls energy metabolism linked to AMPK activation and obesity-associated pathophysiology. Nat Commun. 2018 Sep 10;9(1):3658. doi: 10.1038/s41467 018-05870-6. PMID:30201950|PMCID:PMC6131149

Kate Carroll 2013

  • Carroll KR, Elfers EE, Stevens JJ, McNally JP, Hildeman DA, Jordan MB, Katz JD. Extending Remission and Reversing New-Onset Type 1 Diabetes by Targeted Ablation of Autoreactive T Cells. Diabetes. 2018 Nov;67(11):2319-2328. doi: 10.2337/db18-0204. Epub 2018 Aug 13.PMID:30104248|PMCID:PMC6198341

Rebecca Crowther 2018

  • Lange SM, McKell MC, Schmidt SM, Zhao J, Crowther RR, Green LC, Bricker RL, Arnett E, Köhler SE, Schlesinger LS, Setchell KDR, Qualls JE. l-Arginine Synthesis from l-Citrulline in Myeloid Cells Drives Host Defense against Mycobacteria In Vivo. J Immunol. 2019 Mar 15;202(6):1747-1754. doi: 10.4049/jimmunol.1801569. Epub 2019 Feb 1. PMID: 30710047

Roger Fecher 2010

  • Friedrich D, Zapf D, Lohse B, Fecher RA, Deepe GS Jr, Rupp J. The HIF-1α/LC3-II Axis Impacts Fungal Immunity in Human Macrophages. Infect Immun. 2019 Jun 20;87(7). pii: e00125-19. doi: 10.1128/IAI.00125-19. Print 2019 Jul. PMID:31036602
  • Chowdhury D, Alrefai H, Landero Figueroa JA, Candor K, Porollo A, Fecher R, Divanovic S, Deepe GS Jr, Subramanian Vignesh K. Metallothionein 3 Controls the Phenotype and Metabolic Programming of Alternatively Activated Macrophages. Cell Rep. 2019 Jun 25;27(13):3873-3886.e7. doi: 10.1016/j.celrep.2019.05.093. PMID: 31242420

Johnathan Fletcher 2013

  • Hennigan RF, Fletcher JS, Guard S, Ratner N. Proximity biotinylation identifies a set of conformation-specific interactions between Merlin and cell junction proteins. Sci Signal. 2019 Apr 23;12(578). pii: eaau8749. doi: 10.1126/scisignal.aau8749. PMID:31015291
  • Fletcher JS, Wu J, Jessen WJ, Pundavela J, Miller JA, Dombi E, Kim MO, Rizvi TA, Chetal K, Salomonis N, Ratner N. Cxcr3-expressing leukocytes are necessary for neurofibroma formation in mice. JCI Insight. 2019 Feb 7;4(3). pii: 98601. doi: 10.1172/jci.insight.98601. [Epub ahead of print].PMID:30728335|PMCID:PMC6413799
  • Fletcher JS, Springer MG, Choi K, Jousma E, Rizvi TA, Dombi E, Kim MO, Wu J, Ratner N. STAT3 inhibition reduces macrophage number and tumor growth in neurofibroma. Oncogene. 2019 Apr;38(15):2876-2884. doi: 10.1038/s41388-018-0600-x. Epub 2018 Dec 12. PMID:30542122|PMCID:PMC6461477

Corinne Foley 2016

  • Ernst MM, Chen D, Kennedy K, Jewell T, Sajwani A, Foley C, Sandberg DE; DSD-TRN Psychosocial Workgroup and Accord Alliance. Disorders of sex development (DSD) web-based information: quality survey of DSD team websites. Int J Pediatr Endocrinol. 2019;2019:1. doi: 10.1186/s13633-019-0065-x. Epub 2019 May 28. PMID: 31149017

Shannon Lange 2012

  • Lange SM, McKell MC, Schmidt SM, Zhao J, Crowther RR, Green LC, Bricker RL, Arnett E, Köhler SE, Schlesinger LS, Setchell KDR, Qualls JE. l-Arginine Synthesis from l-Citrulline in Myeloid Cells Drives Host Defense against Mycobacteria In Vivo. J Immunol. 2019 Mar 15;202(6):1747-1754. doi: 10.4049/jimmunol.1801569. Epub 2019 Feb 1. PMID: 30710047

Jennifer Leddon 2010

  • Denton NL, Chen CY, Hutzen B, Currier MA, Scott T, Nartker B, Leddon JL, Wang PY, Srinivas R, Cassady KA, Goins WF, Cripe TP. Myelolytic Treatments Enhance Oncolytic Herpes Virotherapy in Models of Ewing Sarcoma by Modulating the Immune Microenvironment. Mol Ther Oncolytics. 2018 Oct 18;11:62-74. doi: 10.1016/j.omto.2018.10.001. eCollection 2018 Dec 21. PMID:30505937|PMCID:PMC6249791

McKell, Melanie 2017

  • Lange SM, McKell MC, Schmidt SM, Zhao J, Crowther RR, Green LC, Bricker RL, Arnett E, Köhler SE, Schlesinger LS, Setchell KDR, Qualls JE. l-Arginine Synthesis from l-Citrulline in Myeloid Cells Drives Host Defense against Mycobacteria In Vivo. J Immunol. 2019 Mar 15;202(6):1747-1754. doi: 10.4049/jimmunol.1801569. Epub 2019 Feb 1. PMID: 30710047

Zubin Patel 2013

  • Patel ZH, Lu X, Miller D, Forney CR, Lee J, Lynch A, Schroeder C, Parks L, Magnusen AF, Chen X, Pujato M, Maddox A, Zoller EE, Namjou B, Brunner HI, Henrickson M, Huggins JL, Williams AH, Ziegler JT, Comeau ME, Marion MC, Glenn SB, et al, Harley, J.A plausibly causal functional lupus-associated risk variant in the STAT1-STAT4 locus. Hum Mol Genet. 2018 Jul 1;27(13):2392-2404. doi: 10.1093/hmg/ddy140. PMID:29912393|PMCID:PMC6005081

Andrew Patterson 2013

  • Patterson AR, Bolcas P, Lampe K, Cantrell R, Ruff B, Lewkowich I, Hogan SP, Janssen EM, Bleesing J, Khurana Hershey GK, Hoebe K. Loss of GTPase of immunity-associated protein 5 (Gimap5) promotes pathogenic CD4(+) T-cell development and allergic airway disease. J Allergy Clin Immunol. 2019 Jan;143(1):245-257.e6. doi: 10.1016/j.jaci.2018.10.018. Epub 2018 Oct 25. PMID:30616774|PMCID:PMC6327968

Carolyn Rydyznski 2012

  • Rydyznski CE, Cranert SA, Zhou JQ, Xu H, Kleinstein SH, Singh H, Waggoner SN. Affinity Maturation Is Impaired by Natural Killer Cell Suppression of Germinal Centers. Cell Rep. 2018 Sep 25;24(13):3367-3373.e4. doi: 10.1016/j.celrep.2018.08.075. PMID:30257198|PMCID:PMC6192537

Tzu-yu Shao 2016

  • Shao TY, Ang WXG, Jiang TT, Huang FS, Andersen H, Kinder JM, Pham G, Burg AR, Ruff B, Gonzalez T, Khurana Hershey GK, Haslam DB, Way SS. Commensal Candida albicans Positively Calibrates Systemic Th17 Immunological Responses. Cell Host Microbe. 2019 Mar 13;25(3):404-417.e6. doi: 10.1016/j.chom.2019.02.004. PMID:30870622|PMCID:PMC6419754

Anastasiya Slaughter 2018

  • May M, Slaughter A, Lucas D. Dynamic regulation of hematopoietic stem cells by bone marrow niches. Curr Stem Cell Rep. 2018 Sep;4(3):201-208. doi: 10.1007/s40778-018-0132-x. Epub 2018 Aug 2. PMID: 30984517

Presentations

Ayad Ali 2017

  • LAG-3: a potential negative regulator of NK cell immunoregulation during viral infection. Autumn Immunology Conference. Chicago, IL, 2018. (Regional)
  • LAG-3 modulation of NK cell immunoregulatory function. Annual American Association of Immunologists Meeting. San Diego, CA 2019.

Calvin Chan 2015

  • Type I Interferon Sensing Unlocks Dormant Adipocyte Inflammatory Potential. 33rd National MD/PhD Conference, Keystone, CO. 2018

Rebecca Crowther 2018

  • Effect of Lcitrulline supplementation on CD4+ T cell responses during pulmonary Mycobacterium bovis BCG immunization. AAP/ASCI/APSA Annual Meeting, April 2019, Chicago, IL.

KC Sullivan-Locker 2014

  • Functional characterization of an activating anti-TLR4 monoclonal antibody (UT18) with a demonstrated role in reversal of new-onset type I diabetes in NOD mice. Poster presentation at American Association of Immunologists Annual Meeting 2019 May 9-13; San Diego, CA.

McKell, Melanie 2017

  • Graduate Student Expo, University of Cincinnati, OH, February 2019. Poster presentation and abstract
  • Autumn Immunology Conference, Chicago, IL, November 2018. Oral presentation, poster presentation, and abstract
  • Graduate Student Research Forum, UC College of Medicine, OH, October 2018. Poster presentation and abstract
  • IRTG 1911 Allergy Meets Infection, University of Lubeck, Germany, September 2018. Oral presentation, poster presentation, and abstract

Tzu-yu Shao 2016

  • Immunity to Invasive infection by commensal microbes. Gordon Research Conference. Galveston TX
  • Immunity to Invasive infection by commensal microbes. 47th Autumn Immunology Conference, Chicago IL
  • Immunity to Invasive infection by commensal microbes. Annul Immunology Retreat, Cincinnati OH

Anna Sliz 2014

  • The GRB2- associated binding protein 3 is required for IL-2 and IL-15 induced NK cell expansion and limits trophoblast invasion during pregnancy. American Association of Immunologists 103rd Annual Meeting, San Diego, CA, May 9-13, 2019, abstract 591.

Nicholas Weaver 2016

  • Role of KIF16B in HIV-1 Envelope Glycoprotein Trafficking.” Cold Spring Harbor Annual Retrovirology Meeting 2019. Cold Spring Harbor Laboratory, New York. 20 May 2019.

Training Grant - Appointee Accomplishments

Calvin Chan

Degrees

  • BS University of Mary Washington, VA 
  • MS University of Cincinnati, OH 
  • MD/PhD University of Cincinnati, OH *Anticipated*

Mentors

  • PI: Senad Divanovic 
  • Dissertation committee: George Deepe, Kasper Hoebe, Ian Lewkowich, Thomas Inge

Description of Research

Obesity is pandemic. White adipose tissue is an essential contributor to the chronic, low-grade inflammation in obesity and such inflammation plays a central role in metabolic and end-organ sequelae of obesity. However, the reciprocal interplay between adipocyte homeostasis and immune responses in obesity development (weight gain) and pathogenesis of obesity-associated sequelae is poorly understood. This study aims to define novel immune-mediated control of adipocyte inflammatory capacity and its contribution to the pathogenesis of obesity-associated sequelae (emphasis on IFNAR axis), as well as obesity development (emphasis on BAFF/APRIL axis). Interrogation of these avenues may uncover therapeutic targets focused on controlling weight gain and obesity associated morbidity. 

Progress: We are very pleased with our overall progress. Multiple studies that require a long time to carry out have been initiated and are progressing. We have made significant strides in expanding the impact of type I IFN/IFNAR axis-driven uncovering of adipocyte “immune-like” potential including: (a) Adipocyte type I IFN sensing unlocks an “immune-like” gene signature and augments their inflammatory vigor; (b) Non-hematopoietic IFNAR expression contributes to obesity-associated metabolic derangements. In addition, we have shed direct light into how BAFF and APRIL modify obesity development including: (a) Global analysis, via RNA-seq, indicate that BAFF and APRIL augment lipid metabolic processes in adipocytes; (b) BAFF and APRIL are sufficient to induce white adipocyte lipolysis in vitro; (c) BAFF and APRIL are sufficient to augment brown adipocyte energy expenditure in vitro. Combined our findings have suggested novel and intriguing possibilities for the future mechanistic explorations in the intertwined contribution between inflammation and adipocytes. We currently aim to:

Aim 1. Determine mechanisms by which type I IFN/IFNAR axis modifies adipocyte-intrinsic inflammatory vigor 

Aim 2. Define the BAFF/APRIL receptor(s) sufficient for modulation of obesity development

Presentations

  • Digestive Health Center Annual Scientific Symposium - 2018 Autumn Immunology Conference - 2018

Papers

  • Chan, CC et. al. Type I IFN Sensing Unlocks Dormant Adipocyte Inflammatory Potential. (In revision). C.C.C participated in data generation, data analysis, interpretation, the conception and design of the study and wrote the manuscript.
  • Chan CC et. al. J Inflammation and immunity: From an adipocyte's perspective. JICR. Accepted. C.C.C participated in the conception of this review and wrote the manuscript.
  • Chan CC*, Harley ITP* Pet. al. A BAFF/APRIL axis regulates obesogenic-diet induced weight gain. (*denotes equal contribution; In preparation) C.C.C participated in data generation, data analysis, interpretation, the conception and design of the study and wrote the manuscript.
  • Giles DA et. al. 31TUThermoneutral housing exacerbates nonalcoholic fatty liver disease in mice and allows for sex-independent disease modeling.U31T Nat Med. 2017 C.C.C participated in data generation and review of the manuscript.
  • Cappelletti M et. al. 31TDifferential outcomes of TLR2 engagement in inflammation- induced preterm birth.31T J Leukoc Biol. 2017 Dec 28. doi: 10.1002/JLB.3MA0717- 274RR. [Epub ahead of print] PubMed PMID: 29345344. C.C.C participated in data generation, data analysis, interpretation and review of the manuscript.
  • Mukherjee R et. al. NADPH Oxidase 2 modulates inflammatory vigor during non-alcoholic fatty liver disease progression in mice. Hepatology Comm. 2018. C.C.C participated in data generation, data analysis, interpretation and review of the manuscript.
  • Zhang, C et. al. Hepatic Ago2-mediated RNA silencing controls energy metabolism linked to AMPK activation and obesity-associated pathophysiology. Nature Comm. 2018. C.C.C participated in data generation and review of the manuscript.

Workshops

  • Systems Immunology Workshop, Seahorse XF Workshop
  • Career Dev Activities
  • University of Cincinnati Medical Scientist Training Program Annual Spring Retreat
  • University of Cincinnati Immunology Annual Retreat
  • Immunology Graduate Program Journal Club Immunology Graduate Program Weekly Seminar Series
  • Immunology Graduate Program Student-Postdoc Forum
  • Cincinnati Children’s Liver Interest Group Weekly Forum

Seth Reighard

Degrees

  • BS University of Pittsburgh, Pittsburgh, PA
  • MD/PhD Immunology, University of Cincinnati, OH (anticipated)

Mentors

  • PI: Stephen Waggoner
  • Dissertation Committee: William Ridgway, Edith Janssen, Wenhai Shao, George Deepe

Description of Research
Chimeric antigen receptor (CAR) natural killer (NK) cells are emerging as safe and effective cancer therapeutics that diminish many risks associated with CAR T cell therapy. Outside of cancer, the use of CAR NK cells remains unexplored. My dissertation research explores whether CAR NK cells may provide hope for patients with deadly, incurable autoimmune diseases like lupus. We engineered a CAR containing the extracellular domain of programmed death-ligand 1 (PD-L1) to target its receptor, programmed cell death protein 1 (PD-1), which is highly expressed on follicular helper T lymphocytes (TFH  cells) implicated in lupus pathogenesis. We posit that our CAR NK cells will eliminate these cells, reduce autoantibody production, and alleviate lupus.

Progress: We have found that our PD-L1 CAR-expressing NK cells secrete cytokines, degranulate, and kill upon recognizing PD-1+  target cells, including bona fide human TFH cells. While we can differentiate lupus-derived stem cells into functional NK cells, we are working on optimal expression of our CAR in both primary and stem cell-derived NK cells. We are also testing activity of PD-L1 CAR NK cells in humanized mice with lupus-like disease.

Conferences

Autumn Immunology Conference

  • 11/16/18-11/19/18, Chicago IL
  • Oral & poster presentation

Papers

  • Reighard SD, Cranert SA, Rangel K, Ali A, Gyurova I, de la Cruz-Lynch A, Tuazon J, Kottyan LC, Smith DF, Brunner HI, Waggoner SN. Therapeutic targeting of follicular helper T cells with chimeric antigen receptor-expressing natural killer cells. (under review at Cell Reports) Conceptualization, methodology, experimentation, analysis, original draft writing, reviewing & editing.

Other Support

  • Dr. Ralph and Marian Falk Medical Research Trust Catalyst Awards Program
  • NIH grant DA038017

Workshops

  • Cincinnati Children's Annual Immunology Retreat
  • Second place, oral presentation
  • AAI Young Investigator Award

Career Dev Activities

  • U. of Cincinnati Graduate Student Research Forum
  • First place, poster presentation
  • University of Cincinnati Medical Scientist Training Program Annual Spring Retreat
  • University of Cincinnati Immunology Annual Retreat
  • Immunology Graduate Program Journal Club
  • Immunology Graduate Program Weekly Seminar Series
  • Immunology Graduate Program Student-Postdoc Forum

KC Sullivan Locker

Degrees

  • BA College of Wooster, Wooster, OH
  • PhD candidate in Immunology, University of Cincinnati, OH

Mentors

  • PI: Andrew Herr, PhD
  • Dissertation Committee: William Ridgway, MD, Kasper Hoebe, PhD, William Miller, PhD, Rhett Kovall, PhD

Description of Research

A monoclonal antibody (UT18) targeting the TLR4/MD-2 complex shows a novel role in reversal – not simply prevention – of type I diabetes (T1D) disease onset in non-obese diabetic (NOD) mice. However, the molecular mechanism underlying the observed APC tolerance and alleviation of disease phenotypes remains unclear. My thesis project focuses on determining where UT18 is binding; how the TLR4/MD-2 interface and/or receptor clustering is affected; and whether the UT18:TLR4/MD-2 complex contributes to differential receptor trafficking, cellular localization, and signaling activation. These studies have broad implications, as immunotherapies targeting innate immune receptor signaling and trafficking have promise for other autoimmune and inflammatory diseases.

Progress: Using IgE:FcεRI as a model system for proof-of-concept, we established a protocol for a high-throughput, ELISA-based epitope mapping assay.  We are applying the method to identify the epitopes of various anti-CD89 monoclonal antibodies, some of which have unknown epitopes. Once we have completed these experiments, we plan to submit a methods paper that emphasizes the adaptability of this assay.Virtually any monoclonal antibody epitope could be mapped, provided that the target protein can be recombinantly expressed.

With regard to the UT18 project, we have demonstrated that the antibody binds and induces internalization of the TLR4/MD2 receptor.  Our in vitro data supports that UT18 is a mild TLR4 agonist, and we are now trying to understand how intermediate downstream signaling activation may impact the cellular state of APCs in UT18-treated NOD mice.  In collaboration with the Ridgway lab, we are compiling our data with their RNAseq and qPCR data to determine what key experiments remain to nail down potential mechanism(s) of UT18 stimulation.

Lastly, we are continuing to work on insect cell/baculovirus expression of the TLR4 ectodomain and its co-receptor MD-2 for epitope mapping experiments and biophysical characterization of the UT18:TLR4/MD-2 interaction.

Conferences

  • Upcoming: American Association of Immunologists Annual Meeting San Diego, CA; May 9-13, 2019

Papers

  • Sliz A, Locker KCS, Lampe K, Godarova A, Plas DR, Janssen E, Jones H, Herr AB, Hoebe K. The GRB2-associated binding protein 3 is required for IL-2- and IL- 15-induced NK cell expansion and successful pregnancy.
  • Planned papers: Epitope mapping through chemical modification methods paper; Molecular mechanisms underlying UT18:TLR4/MD2 interactions

Other Support

  • R21 AI120084 (PI William Ridgway, MD)

Career Dev Activities

  • Greater Cincinnati Association for Women in Science (AWIS) networking events
  • University of Cincinnati Immunology Annual Retreat
  • Immunology Graduate Program Journal Club
  • Immunology Graduate Program Weekly Seminar Series
  • Immunology Graduate Program Student-Postdoc Forum