I was born and raised in Toronto, Canada and was interested in biomedical research from a young age. My interest in clinical medicine developed more gradually, accelerating with my exposure to animal models of research (mouse, bovine and others). Most of my clinical experience involved small ruminants and dairy cows, while my animal experience in research is comprised primarily of chicken embryo and engineered mouse models of cancer and developmental biology in the lung, gut and mammary gland, and bovine calf models of infectious disease. I have extra curricular interests in home improvement, drama, music, and web/graphic design, and raise backyard chickens and a 13 year old cocker spaniel/eskimo cross.
Hons. B.Sc. (Biochemistry), McMaster University (Hamilton, Ontario, Canada)
My overarching interest in research is centered on animal models of disease that address fundamental cellular mechanisms of morphogenesis and pathogenesis. I am interested to pursue key paradigms in infectious disease, developmental and cancer biology at the cellular level by leveraging tightly-controlled in vivo or explant models, informed by genomic approaches. Using my clinical training I hope to advance these pursuits toward translational research.
My current Ph.D. thesis work is aimed at dissecting the interactions of Human Immunodeficiency Virus (HIV) and Mycobacterium tuberculosis (Mtb) at the cellular and molecular level in primary human macrophages, the nascent hosts for these organisms. While much of the HIV research to date has focused on T-lymphocytes, mucosal macrophages are more recently being appreciated as the key early reservoir for HIV infection prior to seroconversion. Consistent with this notion, emerging data suggests a mutual benefit exists between HIV and Mtb, an observation that may partially explain the high incidence of co-infection in critical human reservoirs, particularly in sub-Saharan Africa. Using transcriptional profiling, RNAi knockdown, synthetic mRNA technology and time lapse imaging, I am investigating the mechanism for this mutual benefit in primary human macrophages, with the aim to expose weaknesses in the relationship that can be exploited with novel therapies. Of importance is the accelerating emergence of highly selected multi- and extensively drug resistant strains of Mtb - both abroad and in the United States - that threaten our ability to contain this infection. On the backdrop of the global HIV epidemic, novel insight of these two pathogens within the host macrophage has become increasingly urgent.
Publications & Presentations
Welsh IC, Thomsen MJ, Gludish DW, Alfonso-Parra C, Bai Y, Martin JF, and Kurpios NA. Integration of left-right Pitx2 transcription and Wnt signaling drives asymmetric gut morphogenesis via Daam2. Developmental Cell. 2013 Sep 30;26(6):629-644. PMID: 24091014 . **COVER ARTICLE**
Kurpios NA, Girgis-Gabardo A, Hallett RM, Rogers S, Gludish DW, Kockeritz L, Woodgett J, Cardiff R, Hassell JA. Single unpurified breast tumor-initiating cells from multiple mouse models efficiently elicit tumors in immune-competent hosts. PLoS One. 2013;8(3):e58151. PMID: 23555570
Lee JH, Kim J, Gludish DW, Roach RR, Saunders AH, Barrios J, Woo AJ, Chen H, Conner DA, Fujiwara Y, Stripp BR, Kim CF. Surfactant protein-C chromatin-bound green fluorescence protein reporter mice reveal heterogeneity of surfactant protein C-expressing lung cells. Am J Respir Cell Mol Biol. 2013 Mar;48(3):288-98. PMID: 23204392
Hamilton BS, Gludish DW, Whittaker GR. Cleavage activation of the human-adapted influenza virus subtypes by matriptase reveals both subtype and strain specificities. J Virol. 2012 Oct;86(19):10579-86. PMID: 22811538
Zacharek SJ, *Fillmore CM, *Lau AN, *Gludish DW, Chou A, Ho JW, Zamponi R, Gazit R, Bock C, Jäger N, Smith ZD, Kim TM, Saunders AH, Wong J, Lee JH, Roach RR, Rossi DJ, Meissner A, Gimelbrant AA, Park PJ, Kim CF. Lung Stem Cell Self-Renewal Relies on BMI1-Dependent Control of Expression at Imprinted Loci. Cell Stem Cell. 2011 Sep 2;9(3):272-81. PMID: 21885022
Kurpios NA, MacNeil L, Shepherd T, Gludish DW, Giacomelli A, and John A. Hassell, 2008. The Pea3 Ets transcription factor regulates differentiation of multipotent progenitor cells during mammary gland development. Dev Bio. Jan 1;325(1):106-21. PMID: 1897734
Gludish DW, Sukumar N, Vignolles M, Stevenson M, and Russell DG. Novel tools to study the synergistic coinfection of M.tuberculosis and Human Immunodeficiency Virus in primary human macrophages. Annual 2013 BBS Research Symposium, Cornell University College of Veterinary Medicine, Ithaca, NY. August 21, 2013. **Third prize poster award.**
Gludish DW and Russell DG. Tools to study the interaction and containment of M.tuberculosis and Human Immunodeficiency Virus in primary human macrophages. DVM 2013 Research Poster Symposium, Cornell University College of Veterinary Medicine, Ithaca, NY. April 11, 2013
Welsh IC, Gludish DW, Alfonso-Parra C, Reis P, Mahadevan A, Martin JF, and Kurpios NA. Integration of Pitx2 transcription and noncanonical WNT signaling controls asymmetric cellular behavior during gut morphogenesis. Cornell Center for Vertebrate Genomics annual symposium, Cornell University, Ithaca, New York. July 12, 2011. **First prize poster award**
Welsh IC, Mahadevan AM, Gludish DW, and Natasza A. Kurpios. Genomic analyses of asymmetric gut development. American Society for Cell Biology. Annual Meeting 2010. Philadelphia, PA. December 11-15, 2010.
Welsh IC, Mahadevan AM, Gludish DW, and Natasza A. Kurpios. Genomic analyses of asymmetric gut tilting. Fifth Biennial Meeting of the American Society for Matrix Biology. Charleston, SC, October 24-27, 2010.
Raiser DM, Gludish, DW, and Carla F. Kim. The role of bronchioalveolar stem cells in lung epithelial repair. Seventy-third Annual Cold Spring Harbor Laboratory Symposium: Control and Regulation of Stem cells, May 28 - June 2, 2008. Cold Spring Harbor, NY.
Gludish, DW, and John A. Hassell. A functional genomics approach to identify novel biomarkers and candidate therapeutic targets of breast tumour-initiating cells cultured in vitro. Canadian Breast Cancer Research Alliance Reasons for Hope conference, May 6-8, 2006. Montreal, Canada.