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Hiroshi Nakagawa, M.D., Ph.D.

Research Associate Professor of Medicine
Department: Medicine
Graduate Group Affiliations

Contact information
Division of Gastroenterology
421 Curie Boulevard
956 Biomedical Research Building
Philadelphia, PA 19104
Office: 215-573-1867
Fax: 215-573-2024
Education:
MD
Okayama University, Okayama, Japan, 1989.
Ph.D.
Okayama University (Medical Science) Okayama, Japan, 1993.
Post-Graduate Training
Resident in Medicine , Okayama University Hospital, Okayama, Japan, 1989-1990.
Clinical Fellow in Gastroenterology and Hepatology, The First Department of Internal Medicine, Okayama University Medical School, Okayama, Japan, 1990-1993.
Postdoctoral Research Fellow, Massachusetts General Hospital, Gastrointestinal Unit, Harvard Medical School, Boston, Mass, 1993-1996.
Postdoctoral Research Fellow, The First Department of Internal Medicine, Okayama University Medical School, Okayama, Japan, 1997-1998.
Certifications
Diplomate, Japanese Board of Internal Medicine, 1999.
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Description of Research Expertise

A major goal of my laboratory is to understand the molecular mechanisms by which the tumor microenvironment fosters esophageal tumor initiation and progression. Currently, I investigate how factors such as hypoxia and transforming growth factor (TGF)-β induce epithelial-to-mesenchymal transition (EMT) in esophageal squamous cell carcinoma (ESCC) cells. In addition, I have been exploring the roles of the Notch signaling in esophageal epithelial homeostasis, malignant transformation and cancer stem cells. Notch signaling and TGF-β regulate cooperatively EMT and foster resistance to conventional chemotherapy. I have a broad background in gastrointestinal epithelial biology, tumor biology, and molecular and cellular biology with specific training and expertise in key research areas.

As a postdoctoral fellow at the Massachusetts General Hospital, I worked on fundamental cell cycle regulation and gene transcription in esophageal squamous epithelial cell model systems, using both in vitro and in vivo approaches. I investigated the transcriptional regulation of viral and cellular promoters that are active in the esophageal epithelium, with the identification of cis-regulatory elements and trans-activating factors, cross-regulating the Epstein-Barr virus ED-L2 promoter and keratin promoters. I used this as a platform for utilizing the EBV ED-L2 promoter to target genes (e.g. cyclin D1) in transgenic mice.

As faculty member at the Gastroenterology Division of the University of Pennsylvania, I expanded my research to include epidermal growth factor receptor (EGFR) oncogene. As PI of several previous university, private (American Gastroenterological Association Research Scholar Award), and NIH-funded grants (K01, K26, R21 and R01), I have developed primary and immortalized human and mouse esophageal epithelial cell culture systems, human tissue engineering in organotypic 3D culture, a form of human tissue engineering, and xenograft transplantation and genetically engineered mouse models coupled with in vivo molecular imaging.

I successfully administered the projects (e.g. staffing, research protections, budget), collaborated with other researchers, and produced several peer-reviewed publications from each project. I have mentored a visiting faculty member, nine postdoctoral research fellows, including young clinician-scientists, and graduate and undergraduate students.

In addition, I serve as Associate Director of Cell Culture Core at the University of Pennsylvania Perelman School of Medicine. We provide a centralized repository of human and mouse-derived normal and engineered as well as cancer cell lines including numerous esophageal and head and neck squamous cell carcinoma cell lines. We also produce retroviruses and lentiviruses for gene transduction experiments, and preparation of organotypic 3D culture substrates (fibroblasts-matrix) and required media.

Selected Publications

Guha M, Srinivasan S, Guja KE, Mejía E, Garcia-Diaz M, F. Brad Johnson FB, Ruthel G, Kaufman B, Rappaport E, Glineburg R, Fang J, Klein-Szanto AJ, Nakagawa H and Avadhani NG: HnRNPA2 is a novel histone acetyltransferase which mediates mitochondrial stress induced nuclear gene expression. Cell Discovery 2017.

Facompre Nicole D, Harmeyer Kayla M, Sole Xavier, Kabraji Sheheryar, Belden Zachary, Sahu Varun, Whelan Kelly, Tanaka Koji, Weinstein Gregory S, Montone Kathleen T, Roesch Alexander, Gimotty Phyllis A, Herlyn Meenhard, Rustgi Anil K, Nakagawa Hiroshi, Ramaswamy Sridhar, Basu Devraj: JARID1B Enables Transit between Distinct States of the Stem-like Cell Population in Oral Cancers. Cancer research 76(18): 5538-49, Sep 2016.

Noguchi Chiaki, Grothusen Grant, Anandarajan Vinesh, Martínez-Lage García Marta, Terlecky Daniel, Corzo Krysten, Tanaka Katsunori, Nakagawa Hiroshi, Noguchi Eishi: Genetic controls of DNA damage avoidance in response to acetaldehyde in fission yeast. Cell Cycle Sep 2016.

Muir Amanda B, Dods Kara, Henry Steven J, Benitez Alain J, Lee Dale, Whelan Kelly A, DeMarshall Maureen, Hammer Daniel A, Falk Gary, Wells Rebecca G, Spergel Jonathan, Nakagawa Hiroshi, Wang Mei-Lun: Eosinophilic Esophagitis-Associated Chemical and Mechanical Microenvironment Shapes Esophageal Fibroblast Behavior. Journal of pediatric gastroenterology and nutrition 63(2): 200-9, Aug 2016.

Whelan Kelly A, Merves Jamie F, Giroux Veronique, Tanaka Koji, Guo Andy, Chandramouleeswaran Prasanna M, Benitez Alain J, Dods Kara, Que Jianwen, Masterson Joanne C, Fernando Shahan D, Godwin Bridget C, Klein-Szanto Andres J, Chikwava Kudakwashe, Ruchelli Eduardo D, Hamilton Kathryn E, Muir Amanda B, Wang Mei-Lun, Furuta Glenn T, Falk Gary W, Spergel Jonathan M, Nakagawa Hiroshi: Autophagy mediates epithelial cytoprotection in eosinophilic oesophagitis. Gut Feb 2016.

Merves Jamie F, Whelan Kelly A, Benitez Alain J, Muir Amanda B, Furuta Glenn T, Wang Mei-Lun, Falk Gary W, Spergel Jonathan M, Nakagawa Hiroshi: ATG7 Gene Expression as a Novel Tissue Biomarker in Eosinophilic Esophagitis. The American journal of gastroenterology 111(1): 151-3, Jan 2016.

Chandramouleeswaran Prasanna M, Shen Dawen, Lee Anna J, Benitez Alain, Dods Kara, Gambanga Fiona, Wilkins Benjamin J, Merves Jamie, Noah Yuliana, Toltzis Sarit, Yearley Jennifer H, Spergel Jonathan M, Nakagawa Hiroshi, Malefyt Rene deWaal, Muir Amanda B, Wang Mei-Lun: Preferential Secretion of Thymic Stromal Lymphopoietin (TSLP) by Terminally Differentiated Esophageal Epithelial Cells: Relevance to Eosinophilic Esophagitis (EoE). PloS one 11(3): e0150968, 2016.

Tanaka Koji, Whelan Kelly A, Chandramouleeswaran Prasanna M, Kagawa Shingo, Rustgi Sabrina L, Noguchi Chiaki, Guha Manti, Srinivasan Satish, Amanuma Yusuke, Ohashi Shinya, Muto Manabu, Klein-Szanto Andres J, Noguchi Eishi, Avadhani Narayan G, Nakagawa Hiroshi: ALDH2 modulates autophagy flux to regulate acetaldehyde-mediated toxicity thresholds. American journal of cancer research 6(4): 781-96, 2016.

Kong Jianping, Sai Hong, Crissey Mary Ann S, Jhala Nirag, Falk Gary W, Ginsberg Gregory G, Abrams Julian A, Nakagawa Hiroshi, Wang Kenneth, Rustgi Anil K, Wang Timothy C, Lynch John P: Immature myeloid progenitors promote disease progression in a mouse model of Barrett's-like metaplasia. Oncotarget Oct 2015.

Maehara Osamu, Sato Fumiyuki, Natsuizaka Mitsuteru, Asano Ayaka, Kubota Yoshimasa, Itoh Jun, Tsunematsu Seiji, Terashita Katsumi, Tsukuda Yoko, Nakai Masato, Sho Takuya, Suda Goki, Morikawa Kenichi, Ogawa Koji, Chuma Makoto, Nakagawa Koji, Ohnishi Shunsuke, Komatsu Yoshito, Whelan Kelly A, Nakagawa Hiroshi, Takeda Hiroshi, Sakamoto Naoya: A pivotal role of Krüppel-like factor 5 in regulation of cancer stem-like cells in hepatocellular carcinoma. Cancer biology & therapy 16(10): 1453-61, Oct 2015.

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Last updated: 12/05/2016
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