Taosheng Huang

Associate Professor & Staff Physician, Pediatrics
School of Medicine

Associate Professor, Pathology
School of Medicine

Associate Professor, Developmental & Cell Biology
School of Biological Sciences

Director, MitoMed Diagnostic Lab
School of Medicine

Director, Cardiovascular Genetic Clinic
School of Medicine

Ph.D., Mount Sinai Medical School, New York, New York, 1991, Biomedical Science


M.D., Fujian Medical College, Fuzhou, Fujian, China, 1983, Pediatrics

Phone: (949) 824-9346
Fax: (949) 824-9776
Email: huangts@uci.edu

University of California, Irvine
314 Sprague Hall
Mail Code: 3950
Irvine, CA 92697

picture of Taosheng  Huang

Research
Interests
Molecular basis of genetic diseases in humans
   
URL www.ucihs.uci.edu/com/pediatrics/drhuang/
   
Academic
Distinctions
1989 Predoctoral Travel Fellowship
American Society of Virology
1990 Third Place SCBA Poster Competition
Society of Chinese Biomedical Scientists in America
1996 Resident Research Award
Georgetown University Hospital
Children’s Medical Center
Washington, DC
1996 Fellowship Training Grant
National Health Institute/Harvard Medical School
Boston, Massachusetts
1998 Farley Fellowship
Children’s Hospital, Boston
Harvard medical School
Boston, Massachusetts
2003 The Second Place of the Research Award
College of Medicine
University of California, Irvine
Irvine, California
1999-2004 Clinical Associate Physician Award
National Health Institute
2004 Junior Physician-Scientist Award
Dean of College of Medicine
University of California, Irvine
Irvine, California
   
Appointments 07/93-07/96 Intern and Resident in Pediatrics
Georgetown University Medical School
Children’s Medical Center
Washington, DC

07/96-07/99 Clinical Fellow in Genetics and Metabolism
Children’s Hospital
Harvard Medical School
Boston, Massachusetts

12/97-07/99 Research Fellow
Seidman Laboratory
Howard Hughes Medical Institute
Harvard Medical School
Boston, Massachusetts
   
Research
Abstract
The primary interest of my lab is to study the molecular basis of genetic syndromes and to apply the discoveries from rare diseases to common conditions. Currently, we are focusing on the following areas:

1. The role of TBX3 in breast cancer TBX3 is a T-box transcription factor. Mutation of TBX3 causes Ulnar-Mammary syndrome, which is characterized by hypoplasia and absence of the mammary gland. We were one of the first groups to show that overexpression of TBX3 plays an important role in breast cancer. We have analyzed TBX3 expression in human breast cancer tissue. The TBX3 expression levels were compared with those of matched normal tissues from the same individual and correlated with other established biomarkers. Our study shows that TBX3 is overexpressed in primary breast cancer tissues. Mechanistically, we found that TBX3 interacts with HDACs and inhibit the downstream target gene expression. In addition, we found TBX3 regulates a large group of genes in breast cancer. Our current research aims to optimize the clinical relevance of this data and we work with animal and breast cancer tissues in parallel. Recently, we also found TBX3 plays a very important role in hES cell differentiation, which will facilitate our understanding of TBX3 functions.

2. The Genetic basis of optic atrophy We have identified many families with autosomal dominant inherited optic atrophy. We reported that some mutations of the OPA1 gene can cause a sex-influenced phenotype; the males are more severely affected and have an earlier onset as compared to the female members of the family. This human study leads to another interesting discovery. In collaboration with Dr. Arnold Star in the Department of Neurology, we found the OPA1 mutation H445R causes loss of vision and hearing. Using electrophysiological analysis, we found that this mutation causes asynchronous cochlear conduction and this suggests a novel mechanism of optic atrophy. To study the function of OPA1 and the molecular mechanisms of optic atrophy, we created a drosophila model for OPA1. We found that homozygous OPA1 knockout was lethal, but we circumvented this by generating a somatic mutation with an eye flipase. In adult flies, the dOpa1 somatic mutation caused an increase in reactive oxygen species (ROS) production and mitochondrial fragmentation, and these were associated with loss of and damage to the cone and pigment cells. Our group went on to show that antioxidants can partially reverse the glossy eye phenotype, further suggesting that ROS play an important role in cone and pigment cell death. Together, these results show dOpa1 mutations cause cell loss by two distinct pathogenic pathways. This study provides novel insights into the pathogenesis of optic atrophy and demonstrates the promise of antioxidants as therapeutic agents for this condition.

3. To identify the disease-causing gene associated with noncompaction of the ventricular myocardium (spongy heart), we are studying a family with balanced translocation with this condition, and are also performing a linkage study for a large family with this disease.

4. The intracellular pathway to study TBX5. TBX5 is a T-box transcription factor. Mutations of TBX5 cause Holt-Oram syndrome characterized by congenital heart diseases and limb anomalies. By studying the intracellular network of TBX5, including the upstream transcription factor that controls TBX5 expression cofactor that interacts with TBX5 and downstream target whose genetic regulation is dependent on TBX5. We anticipate identifying many genes associated with congenital heart disease, a most common malformation in humans, and contribute significantly to the mobility and mortality in pediatric populations.
   
Publications Selected peer-reviewed publications (in chronological order)

5. Taosheng Huang, Peter Palese and Mark Krystal, Determination of influenza virus proteins required for genome replication. Journal of Virology 64:5669-5673, 1990

6. Yi Chu, Taosheng Huang and Ming-Ta Hsu, P1 nuclease defines a subpopulation of active SV40 chromatin-- a new nuclease hypersensitivity assay. Nucleic Acid Research 18:3705-3711, 1990

7. Taosheng Huang and Ming-Ta Hsu, Inhibition of DNA replication of adenovirus type 5 and Simian virus 40 by tunicamycin. Virology, 182:889-893, 1991

8. Kyeon H. Park, Taosheng Huang, Fred F. Correia and Mark Krystal, Rescue of a synthetic gene into Sendai virus. Proceedings of the National Academy Sciences of the USA, 88:5537-5541, 1991

9. Taosheng Huang, Jovan Pavloic, Peter Staeheli and Mark Krystal, Overexpression of the influenza polymerase protein can titrate out inhibition by the murine Mx1 protein. Journal of Virology, 66:4154-4160, 1992

10. Taosheng Huang, Ellen Elias, John B Mulliken, Daniel J Kirse and Lewis B Holmes, A new syndrome: cardiac defects, Laryngeal anomalies, preaxial polydactyly, and colonic aganglionosis in sibs. Genetics in Medicine, 1(3):104-108, 1999

11. Craig T Basson, Taosheng Huang, Robert Lin, David R Bachinsky, Stanislawa Weremowicz, Alicia Vaglio, Rina Bruzzone, Roberto Quadrelli, Margherita Lerone, Giovanni Romeo, Margherita Silengo, Cynthia C Morton, Christoph W Muller, JG Seidman, Christine E Seidman, 1998, Different TBX5 interactions in heart and limb defined by Holt-Oram syndrome. Proceedings of the National Academy Sciences of the USA, 96:2919-2924, 1999

12. Taosheng Huang, Wenxue Yang, Alexandre Pereira, Vivian E Shih, Cloning and characterization of a putative human 2-hydroxylacid dehydrogenase, Biophysica Biochemica Research Communication, 268:298-301, 2000
13. Taosheng Huang, Stanislawa Weremowicz, Angela E. Lin, Gerry Cox, Wendy L. Golden, Mitsuhiro Kamisago, Gerald L. Feldman, Stefan Vermeulen, Moog Ute, Connie Schrander-Stumpel; Variable Cardiac Phenotypes in Chromosome 4q- Syndrome with dHAND Deletion, Genetics in Medicine, 4(6) 464-467, 2002

14. Taosheng Huang & Mark Korson, Celeste Krauss, Lewis B. Holmes, A New Genetic Syndrome: Four Cases with Encephalocele, triphalangeal thumb, American Journal of Medical Genetics 111:178-181, 2002

15. Helen M. Lyon, Lewis Holmes and Taosheng Huang; Multiple congenital anomalies associated with in utero exposure phynotoin support hypoxic ischemic mechanisms Birth Defects Research part A, 67: 993-996, 2003

16. Drapkin RI, Genest DR, Holmes LB, Huang T, Vargas SO. Unilateral transverse arm defect with subterminal digital nubbins. Ped Devel Pathol. 6(4) 348-354, 2003

17. Guifeng Sun Lisa E Lewis, Xu Huang, Quang Nguyen, Christopher Price, Taosheng Huang, Tbx5, A Gene Mutated In Holt-Oram Syndrome, Is Regulated through a GC-Box and TBEs, Journal of Cellular Biochemistry, 92(1):189-99, 2004

18. Mike Zaragoza, Lisa E. Lewis, Guifeng Sun, Eric Wang, Ling Li, Ilham Said-Salman, Laura Feucht, Taosheng Huang, Identification of the TBX5 Transactivating Domain And the Nuclear Localization Signal, Gene, 2004, 330:9-18

19. Weiwei Fan, Xu Huang, Chira Chen, Joe Gray and Taosheng Huang (2004) TBX3 and TBX3+2a are Functionally Distinctive in Inhibition of Senescence and are Overexpressed in a Subset of Breast Cancer Cell Lines, Cancer Research, 64(15):5132-9

20. Taosheng Huang, Jong-Dae Whong, Virginia Kinonis (2006) Sex-Influenced Autosomal Dominant Optic Atrophy is Caused by Mutations of IVS9 +2A>G in The OPA1 Gene, Genetics in Medicine, 8(1):59

21. Roberto Quadrelli, Eugen M. Strehle, Alicia Aaglio, Mariela Larrandaburu, Búrix Mechoso, Andrea Quadrelli, Yao-shan Fan, Taosheng Huang (2007) A girl with del(4)(q33qter) and occipital encephalocele: clinical description and molecular genetic characterization of a rare patient, Genetic Testing,11(1):4-10

22. Hongfei Pan, Guifang Long, Qiang Li, Yanni Feng, Zhiying Lei, Hongwei Wei, Yueyan Huang, Jinghong Huang, Na Lin, Qunqing Xu, Shaiyong Ling, Xiajing Chen, Taosheng Huang (2007) Current Status of Thalassemia in Minority Populations in Guanxi, China, Clinical Genetics, 71: 419–426

23. Andrea Quadrelli, Alicia Vaglio, Roberto Quadrelli, Burix Mechoso, Yao-Shan Fan, Taosheng. Huang (2007) High Density Array Comparative Genomic Hybridization analysis and Follow-up of a child with a De Novo Complex Chromosome Rearrangement detected prenatally, Prenat Diagn. 27(10):982-3

24. Shaohua Tang, Qimin Xu, Xueqin Xu, Xiaomei Yang, Xiaoqin Wang, Nancy Speck, Taosheng Huang (2007) A novel missense mutation in the RUNX2 gene causes cleidocranial dysplasia in a Chinese family with hyperplastic nails, BMC Medical Genetics, BMC Med Genet. 8:82.

25. Will Yarosh, Jessica Monserrate, James Jiayuan Tong, Diane Le, Kimberly Nguyen, Carrie Brachmann Douglas Wallace, Taosheng Huang (2008) The Molecular Mechanisms of OPA1-Mediated Optic Atrophy in Drosophila Model and Prospects for Antioxidant Treatment, PLoS Genetics, 2008 Jan;4(1):e6.

26. Will Yarosh*, Tomasa Barrientos*, Taraneh Esmailpour, Limin Lin, Philip M. Carpenter, Kathryn Osann, Hoda Anton-Culver and Taosheng Huang (2008) TBX3 is overexpressed in breast cancer and represses p14ARF by interacting with HDACs, Cancer Research, 68:693-699 *These authors contribute equally

27. Yongjun Luo, Wenxiang Gao, Yuqi Gao, Sha Tang, Qingyuan Huang, Xiaoling Tan, Jian Chen, Taosheng Huang, 2008 Mitochondrial Genome Analysis of Ochotona curzoniae and Implication of Cytochrome c Oxidase in Hypoxic Adaptation, Mitochondrion, 8 (2008) 352–357

28. Sha Tang, Stephanie Tse, Phung Khanh Le, Kimberly Nguyen, Douglas C. Wallace and Taosheng Huang, 2009, Heterozygous Mutation of Opa1 in Drosophila Shorten Lifespan Mediated through Increased Reactive Oxygen Species Production, PLoS One,4(2):e4492

29. Xianhe Xie, Avetis Boyadjian, Xianhe Xie, Taosheng Huang, 2009 Mutation Analysis of TBX5 in Families with Holt-Oram Syndrome: A Compound Heterozygous Mutation in TBX5, in press

30. Sha Tang, Sumita Danda, Mehrdad Zoleikhaeian, Mariella Simon, Taosheng Huang, An Indian Boy with Nephropathic Cystinosis: A Case Report and Molecular Analysis of CTNS Mutation, Genetic testing and Molecular Biomarkers, 2009, 13 (4): 435–438

31. Parvin Shojaeian, Hung-Tat Leung, Karen Ocorr, Rolf Bodmer, William L. Pak, Stephanie Tse, Phung Khanh Le, Kimberly Nguyen, Taosheng Huang, Heterozygous mutation of Drosophila Opa1 causes the development of multiple organ abnormalities in an age-dependent and organ-specific manner, PLoS One. 4(8):e6867

32. Taosheng Huang, Rosamaria Santarelli, Arnold Starr. Cochlear potentials accompanying R445H mutation of OPA1 gene in patients with both optic and auditory neuropathies, Brain Research, 2009;1300:97-104

33. Luo, Y., Tang, S., Taosheng Huang*, and Gao, Y. Genotyping mitochondrial DNA single nucleotide polymorphisms by PCR ligase detection reactions, (* co-corresponding author) Clinical Chemistry and Laboratory Medicine, 2010;48(4):475-83.

34. Sha Tang., and Taosheng Huang. Parallel sequencing for human mitochondrial DNA characterization and heteroplasmy quantification, Biotechniques, 2010; 48 (4):287–296

35. Sha Tang, Anjan Batra, Yu Zhang, Eric S Ebenroth, Taosheng Huang, 2010, Mutations of the mitochondrial genome are associated with left ventricular noncompaction (LVNC), Mitochondrion, 10(4):350-7

Reviews Articles

1. Taosheng Huang (2002) Current advances in Holt-Oram syndrome, Curr Opin Pediatr. 14(6):691-5

2. Taosheng Haung, Ming Qi (2005) Report ? 21st century medical genetic and genomic medicine in China, Journal of Zhejian University Science B, 6(12): 1223-1226

3. Sha Tang, Taosheng Huang (2008) Genetics of Cardiac Malformations, Review, Journal of Maternal Fetal Medicine, 19:2105-118

4. Taraneh Esmailpour and Taosheng Huang (2008), Advancement in mammary stem cell research, review, J. Cancer Mol. 4(5): 131-138

Meeting Symposium

1. Taosheng Huang, James E Lock, Audrey C Marshall, Craig Basson, J.G. Seidman, Christine E. Seidman (2003) Causes of Clinical Diversity in TBX5 Mutations Cold Spring Harbor Quantitative Biology Symposium, LXVII 115-120

Book Chapters

2. Frank M. LaFerla, Taosheng Huang, Charles J. Bieberich, and Gilbert Jay Transgenic Strategy for Studying Viral Pathogenesis Page 89-106, Chapter 5 in Strategies in transgenic animal science - by Glenn Michael Monastersky, James M. Robl - 1995 - Science press, Washington, DC 20005

3. Taosheng Huang, Steve Keiles, 2009, Approach to single gene disorders in Textbook of Clinical Pediatrics, 2nd edition- by Abdelaziz Y. Elzouki, Springer
   
Grants National Cancer Institute R01CA121876 (PI: T Huang), 2007-2011 Intracellular Network of TBX3 in breast cancer
   
NIH-National Cancer Institute, 1R01CA121876 (PI: T Huang) 08/01/2008-06/30/2011 Title: The role of TBX3 in Human Embryos Stem Cell Differentiation Minority Supplement for Taraneh Esmailpour
   
National Eye Institute 1R01EY018876, 04/01/08-3/30/13 (PI : T Huang) Genetics Studies of Optic Atrophy
   
Larry & Helen Hoag Foundation (PI: T Huang) 07/01/2005-12/30/2010 Title: Studies of the TBX5 targets
   
Professional
Societies
Fellow, American College of Medical Genetics, 2003-
American Society of Human Genetics
American Association for Advancement of Science
American Academy of Pediatrics
Medical Director & Board Director
American Chinese Medical Association (ACMA) 1998-2001
Vice President of ACMA, New England Area, 1998-2000
   
Other Experience Attending Physician and Assistant in Medicine
Children's Hospital, Harvard Medical School 1999—2001

Instructor in Genetics
Children's Hospital, Harvard Medical School 1999—2001

American Board of Pediatrics
1996

American Board of Medical Genetics Clinical Genetics
1999

American Board of Medical Genetics Clinical Molecular Genetics
1999

Graduate Programs Developmental Biology and Genetics

Cancer Biology

Cellular and Molecular Biosciences

   
Research Centers Center for Molecular and Mitochondrial Medicine and Genetics (MAMMAG)
   
Cancer Research Institute
   
Chao Family Cancer Center
   
Center for Developmental and Cell Biology
   
Genetic Epidemiology Research Institute
   
   
Link to this profile http://www.faculty.uci.edu/profile.cfm?faculty_id=5072
   
Last updated 02/13/2014