Physicians and Surgeons Building Room 4-443 Tel 212.305.1048 Email mh29@columbia.edu
	RESEARCH THEME: Mitochondrial and Other Neuromuscular Diseases Using molecular genetic techniques, my laboratory focuses on identifying the causative mutations in neurogenetic diseases and on elucidating how the mutations disrupt normal cellular functions. For more than ten years, I have been studying a rare inherited mitochondrial disease called mitochondrial neurogastrointestinal encephalomyopathy or MNGIE, a fatal degenerative disease characterized by impaired eye movements, severe gastrointestinal symptoms leading to weight loss, and degeneration of motor and sensory nerves. We identified causative mutations in the gene encoding thymidine phosphorylase in MNGIE patients. In this disease, loss of thymidine phosphorylase activity leads to toxic accumulations of molecules that lead to damage in mitochondrial DNA. We are testing potential therapies for this disease. We also identified causative mutations for Danon disease and deficiency of coenzyme Q10. We are currently looking for mutations that cause specific types of muscular dystrophy. I am collaborating with Drs. Hiroshi Mitsumoto, Paul Gordon, and Ali Naini who are looking for a genetic modifier that seems to make women more likely to develop amyotrophic lateral sclerosis in a family with an unusual mutation in superoxide dismutase 1 (SOD1). BACKGROUND AND EDUCATION : Michio Hirano is an Associate Professor of Neurology and Co-Director of the Columbia Muscular Dystrophy Association clinic (Dr. Hiroshi Mitsumoto, Director). He received his M.D. from the Albert Einstein College of Medicine and did his internship at the affiliated Bronx Municipal Medical Center. He did his Neurology Residency at Columbia-Presbyterian Medical Center and was a Chief Resident in his last year. He did a neuromuscular research fellowship under Drs. Salvatore DiMauro and Eric Schon at the H. Houston Merritt Clinical Research Center at Columbia-Presbyterian Medical Center where he became an Assistant Professor of Neurology in 1992. EDUCATION AND TRAINING: 1982 A.B., Harvard College 1986 M.D., Albert Einstein College of Medicine 1986-87 Medical Center Medical Internship, Bronx Municipal Medical Center 1987-90 Neurology Residency, Columbia-Presbyterian Medical Center 1989-90 Chief Resident, Columbia-Presbyterian Medical Center 1990-92 Neuromuscular Research Fellowship, Columbia-Presbyterian Medical Center HONORS AND AWARDS : 1982 A.B. in Biology, magna cum laude, Harvard College 1996-99 Irving Assistant Professor of Neurology, Columbia University 2000-2004 Scientific Committee, Telethon Italia 2002- Nerve and Muscle Section Editor, Current Neurology and Neuroscience Reports 2003- Medical Advisory Committee, Muscular Dystrophy Association SELECTED PUBLICATIONS : Hirano M, Yebenes J, Jones AC, Nishino I, DiMauro S, Carlo JR, Bender AN, Hahn AF, Salberg LM, Weeks DE, Nygaard TG (1998) Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) syndrome maps to chromosome 22q13.32-qter. Am J Hum Genet 63:526-533 Nishino I, Spinazzola A, Hirano M (1999) Thymidine phosphorylase gene mutations in MNGIE, a human mitochondrial disorder. Science 283:689-692 Nishino I, Fu J, Tanji K, Yamada T, Shimojo S, Koori T, Mora M, Riggs JE, Oh SJ, Koga Y, Sue CM, Yamamoto A, Morakami N, Shanske S, Byrne E, Bonilla E, Nonaka I, DiMauro S, Hirano M (2000) Primary lamp-2 deficiency causes X-linked vacuolar cardiomyopathy and myopathy (Danon's disease). Nature 406:906-910 Nishigaki Y, Martí R, Copeland WC, Hirano M (2003) Site-specific mtDNA point mutations due to thymidine phosphorylase deficiency. J Clin Invest 111:1913-1921 Palenzuela L, Andreu A, Gamez J, Vilà MR, Kunimatsu T, Meseguer A, Cervera C, Fernandez Cadenas I, van der Ven PFM, Nygaard TG, Bonilla E, Hirano M (2003) A novel autosomal dominant limb-girdle muscular dystrophy (LGMD 1F) maps to 7q32.1-32.2. Neurology 61:404-406 Quinzii CM, Kattah AG, Naini A, Akman HO, Mootha VK, DiMauro S, Hirano M (2005) Coenzyme Q deficiency and cerebellar ataxia associated with an aprataxin mutation. Neurology 64:539-541		IMAGE 1 Click image to enlarge. IMAGE 2 Click image to enlarge. IMAGE 3 Click image to enlarge. IMAGE 4 Click image to enlarge.

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