Hiroshi Nakagawa

faculty photo
Research Associate Professor of Medicine
Department: Medicine

Contact information
Division of Gastroenterology
421 Curie Boulevard
956 Biomedical Research Building
Philadelphia, PA 19104
Office: 215-573-1867
Fax: 215-573-2024
Graduate Group Affiliations
Okayama University, Okayama, Japan, 1989.
Okayama University (Medical Science) Okayama, Japan, 1993.
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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.

Description of Itmat Expertise

Esophageal cancers
Tumor microenvironment
Notch signaling

Selected Publications

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.

Kinugasa H, Whelan K A, Tanaka K, Natsuizaka M, Long A, Guo A, Chang S, Kagawa S, Srinivasan S, Guha M, Yamamoto K, St Clair D K, Avadhani N G, Diehl J A, Nakagawa H: Mitochondrial SOD2 regulates epithelial-mesenchymal transition and cell populations defined by differential CD44 expression. Oncogene 34(41): 5229-39, 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.

Kong Jianping, Whelan Kelly A, Laczkó Dorottya, Dang Brendan, Caro Monroig Angeliz, Soroush Ali, Falcone John, Amaravadi Ravi K, Rustgi Anil K, Ginsberg Gregory G, Falk Gary W, Nakagawa Hiroshi, Lynch John P: Autophagy levels are elevated in barrett's esophagus and promote cell survival from acid and oxidative stress. Molecular carcinogenesis Sep 2015.

Srinivasan S, Guha M, Dong D W, Whelan K A, Ruthel G, Uchikado Y, Natsugoe S, Nakagawa H, Avadhani N G: Disruption of cytochrome c oxidase function induces the Warburg effect and metabolic reprogramming. Oncogene Jul 2015.

Long Apple, Giroux Véronique, Whelan Kelly A, Hamilton Kathryn E, Tétreault Marie-Pier, Tanaka Koji, Lee Ju-Seog, Klein-Szanto Andres J, Nakagawa Hiroshi, Rustgi Anil K: WNT10A promotes an invasive and self-renewing phenotype in esophageal squamous cell carcinoma. Carcinogenesis 36(5): 598-606, May 2015.

Jiang Ming, Ku Wei-Yao, Zhou Zhongren, Dellon Evan S, Falk Gary W, Nakagawa Hiroshi, Wang Mei-Lun, Liu Kuancan, Wang Jun, Katzka David A, Peters Jeffrey H, Lan Xiaopeng, Que Jianwen: BMP-driven NRF2 activation in esophageal basal cell differentiation and eosinophilic esophagitis. The Journal of clinical investigation 125(4): 1557-68, Apr 2015.

Li Yan, Chitnis Nilesh, Nakagawa Hiroshi, Kita Yoshiaki, Natsugoe Shoji, Yang Yi, Li Zihai, Wasik Mariusz, Klein-Szanto Andres J P, Rustgi Anil K, Diehl J Alan: PRMT5 is required for lymphomagenesis triggered by multiple oncogenic drivers. Cancer discovery 5(3): 288-303, Mar 2015.

Merves Jamie, Chandramouleeswaran Prasanna Modayur, Benitez Alain J, Muir Amanda B, Lee Anna J, Lim Diana M, Dods Kara, Mehta Isha, Ruchelli Eduardo D, Nakagawa Hiroshi, Spergel Jonathan M, Wang Mei-Lun: Altered esophageal histamine receptor expression in Eosinophilic Esophagitis (EoE): implications on disease pathogenesis. PloS one 10(2): e0114831, 2015.

Kikuchi Osamu, Ohashi Shinya, Nakai Yukie, Nakagawa Shunsaku, Matsuoka Kazuaki, Kobunai Takashi, Takechi Teiji, Amanuma Yusuke, Yoshioka Masahiro, Ida Tomomi, Yamamoto Yoshihiro, Okuno Yasushi, Miyamoto Shin'ichi, Nakagawa Hiroshi, Matsubara Kazuo, Chiba Tsutomu, Muto Manabu: Novel 5-fluorouracil-resistant human esophageal squamous cell carcinoma cells with dihydropyrimidine dehydrogenase overexpression. American journal of cancer research 5(8): 2431-40, 2015.

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Last updated: 10/26/2015
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