Durai Subramani Ph.D.


BIOGRAPHICAL SKETCH Provide the following information for the Senior/key personnel and other significant contributors. Follow this format for each person. DO NOT EXCEED FIVE PAGES. NAME: Durai B. Subramani eRA COMMONS USER NAME (credential, e.g., agency login): babu7 POSITION TITLE: Research Associate EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency training if applicable. Add/delete rows as necessary.) INSTITUTION AND LOCATION DEGREE (if applicable) Completion Date MM/YYYY FIELD OF STUDY University of Madras, Chennai, India B.Sc. 03/1997 Biochemistry University of Madras, Chennai, India M.Sc. 09/1999 Biochemistry (SSI) Private Limited, Chennai, India PGDCA. 03/2001 Diploma in Computer Applications University of Madras, Chennai, India Ph.D. 06/2006 Mucins Biology A. Personal Statement Trained as a mucins and mucus biologist, my primary interests lie in understanding how airway mucus clearance is regulated in health and why it fails in chronic obstructive pulmonary diseases such as cystic fibrosis, COPD and asthma. Particularly in CF, airway mucus obstruction is commonly associated with rapid lung decline and permanent damage to the lungs. It is critical to better understand the formation of mucus plaques, how to prevent their occurrence and how to remove them from the lungs. The goal of the proposed research is to examine the role of MUC5B and MUC5AC in the biochemical and biophysical properties of airway mucus. Cough and cilia-dependent mucus flow are controlled by differing adhesion strengths between the mucus layer and the periciliary gel layer. This adhesion is controlled largely by mucus concentration and is thought to be modified by the relative MUC5B to MUC5AC ratio. The aim of our project is to characterize the properties of MUC5AC versus MUC5B, with respect to mucus biophysical properties and mucus flow (e.g., transport). Given my extensive training in mucin biology, I feel confident to have the necessary expertise to successfully carry out the proposed work. During my Ph.D., I studied gastric mucins (MUC2, MUC5AC and MUC6) and explored their role in gastric cancer as a biomarker under the supervision of Dr. Halagowder. As a postdoctoral fellow at Mayo Clinic mentored by Dr. Dr. Mukherjee & Dr. Gendler, I characterized the mechanisms underlying MUC1 over-expressed pancreatic cancer. At the University of Gothenburg mentored by Dr. Dr. Hansson, I revealed how MUC2 is cleaved by bacterial proteases. At Chapel Hill mentored by Drs. Lai, Boucher and Ehre, I studied the role of cervical mucus (i.e., MUC5B) in trapping virus (e.g., HIV, HSV, H1N1) by means of mucosal antibodies(IgG) and I learned about mucin-producing cell cultures, mucin KO mouse models and I successfully conducted mucin genome editing using the CRISPR/Cas9 method. As shown in preliminary data, I generated critical biological models of A549 and Calu-3 cells that are knocked out for MUC5B or MUC5AC expression and CFTR in HT29 cells, which provide a unique tool to study these mucins and mucus. In addition, I have produced several peer-reviewed publications on relevant research topics related to this project. In summary, I have a good record of accomplishments and productivity in pertinent research areas of mucin biology, which makes me a well-qualified candidate to conduct the proposed project. In addition, I am genuinely excited about the possibility to advance my career and become an independent investigator in the field of mucin and mucus research. I believe that this project provides me with a unique opportunity to pursue my career goals while applying the knowledge I gained during my training. Most importantly, this project is an ideal combination of basic and translational research designed to gain better insights in human lung disease pathogenesis, particularly in CF, while investigating potential new therapies. B. Positions and Honors Positions and Employments: 2017- : Research Associate, Department of Cystic Fibrosis Research and Treatment Center, School of Medicine, University of North Carolina at Chapel Hill, NC, USA. 2014-2017: Postdoctoral Fellow, Cystic Fibrosis Center, University of North Carolina at Chapel Hill, NC, USA. 2011-2014: Postdoctoral Fellow, Molecular Pharmaceutics, University of North Carolina at Chapel Hill, NC, USA. 2008-2011: Postdoctoral Fellow, Department of Biochemistry and Molecular Biology, University of Gothenburg, Sweden. 2006-2008: Postdoctoral Fellow, Department of Biochemistry and Molecular Biology, Mayo Clinic, USA. 2001-2006: PhD student, Unit of Biochemistry, Department of Zoology, University of Madras, Chennai, India. Honors and Awards: 2010 Participated in the Nobel Prize Award Ceremony at the Stockholm Concert Hall, Sweden. 2007 Selected for AACR WORKSHOP:Pathobiology of Cancer: The Edward A. Smuckler Memorial Workshop held at Snowmass Resort Village Snowmass, Colorado, U.S.A. 2005 Best poster award at the 46th Annual Conference of the Indian Society of Gastroenterology, Poster entitled as 'MUC2 and Sialyl-Tn are molecular marker in Helicobacter pylori infected pre-neoplastic human gastric epithelium'. Visakhapatnam, Andhra Pradesh. India. 2005 Awarded the "Young Investigator Award" at the 46th Annual Conference of the Indian Society of Gastroenterology. Paper entitled as 'Expression profile of mucin carbohydrate antigens (Sialyl-Lewisa, Sialyl-Lewisx, Sulfo-Lewisa and Sialyl-Tn) in normal, Helicobacter pylori infected pre-neoplastic and neoplastic human gastric epithelium' Visakhapatnam, Andhra Pradesh. India. 2004 - 2006 Awarded Research Fellowship from Lady Tata Memorial Trust, Mumbai, India. (LTMT), Project: Pathogenic role of Helicobacter pylori on mucins and carbohydrates in human gastric epithelium. Mumbai, India, for pursuing Ph.D. Program. 2004 Best poster award at the 45th Annual Conference of the Indian Society of Gastroenterology, November 2004. Poster entitled as 'Expression profile of mucins (MUC2, MUC5AC and MUC6) in Helicobacter pylori infected - pre-neoplastic and neoplastic human gastric epithelium'. Ooty, Tamil Nadu. India 2003 Best poster award at the 44th Annual Conference of the Indian Society of Gastroenterology, December 2003. Poster entitled as 'Adherence of Helicobacter pylori to MUC5AC mucin in human gastric epithelium'. Chennai, Tamil Nadu. India. Other Experience and Professional Memberships 2014- Member, Sigma Xi 2013- Editorial Advisory Board - Oncology, Gastroenterology and Hepatology Reports. C. Contribution to Science: Aside from my present interest as described in the application, my overall research background can be divided into five main research projects including my PhD Thesis, all closely relevant to mucins and mucus in health and diseases. The full bibliography can be found at: http://scholar.google.com/cita... Graduate Thesis: These studies involved the expression profile of mucins (MUC1, MUC2, MUC4, MUC5AC & MUC6) and mucins carbohydrate antigens (Sialyl-LewisX, Sialyl-LewisA, Sialyl-Tn & Sulfo-LewisA) in Helicobacter pylori infected pre-neoplastic and neoplastic human gastric epithelium and the potential role in malignancy. I showed that MUC2 and Sialyl-Tn are the early molecular markers for Helicobacter pylori-mediated gastric carcinogenesis, and conversion of neutral mucins to acidic mucins in gastric and gallbladder cancer. Publications: 1. Durai B. Subramani., Jayanthi, V., Niranjali, D., Reis, C.A. and Devaraj, H., Expression profile of mucins (MUC2, MUC5AC and MUC6) in Helicobacter pylori infected pre-neoplastic human gastric epithelium. Molecular Cancer 2006; 19; 5(1):10(citations:85, impact factor 5.4). 2. Iniya M. Ganesh, Durai B. Subramani and Halagowder Devaraj, Mucin glycoarray in gastric and gallbladder epithelia. Journal of Carcinogenesis 2007;6:10 (citations:19, impact factor 2.32). Book Chapter: 1. Helicobacter pylori-Infected Neoplastic Gastric Epithelium: Expression of MUC2 as a Biomarker (2010) Halagowder Devaraj, A. Anand Kumar and Niranjali Devaraj Methods of Cancer Diagnosis, Therapy and Prognosis, 1, Volume 3, Gastrointestinal Carcinoma, III, Pages 121-136 (two figures are from Durai B. Subramani 2006, doctoral thesis). Project one: Role of MUC1 in pancreatic cancer: My first year of work was mainly focused on showing that overexpression of MUC1 during carcinogenesis leads to higher levels of COX-2, IDO, and B7H4 (all potent immune tolerizing proteins) than tumors without MUC1. I learned many aspects of tumor evasion and showed that the overexpression of MUC1 during carcinogenesis may play a role in: (1) the conversion of CD4+ T cells into T-regulatory (Tregs) cells, (2) the overexpression of cyclooxygenase 2 (COX-2), and (3) the regulation of indoleamine 2,3-dioxygenase (IDO). During my second year I was mainly working on pancreatic cell lines namely BxPc3 and SuSu8686. Interestingly we found that over expression of MUC1 in these cell lines resulted in different morphology of the cells, which has become a novel mechanism called epithelial to mesenchymal transition by MUC1. The preclinical data provide the rationale to design clinical trials with a combination of MUC1-based vaccine, celecoxib, and gemcitabine for the treatment of pancreatic cancer. Publications: 1. Teresa L. Tinder, Durai B. Subramani*, Gargi D. Basu*, Judy M. Bradley, Jorge Schettini, Arefayene Million, Todd Skaar, and Pinku Mukherjee., MUC1 Enhances Tumor Progression and Contributes Toward Immunosuppression in a Mouse Model of Spontaneous Pancreatic Adenocarcinoma. J Immunol. 2008;181(5):3116-25 (citations:86, impact factor 5.36). *Both authors contributed equally to this work. 2. Pinku Mukherjee, Gargi D. Basu, Teresa L. Tinder, Durai B. Subraman