Jing Huang
Professor, Molecular and Medical Pharmacology, University of California Los Angeles
jinghuang@mednet.ucla.edu
(310) 825-4329
Laboratory Address:
23-231 CHS
650 Charles E. Young Drive South
Los Angeles, CA 90095
Lab Number:
(310) 206-3619
Office Address:
23-231A CHS
Department of Molecular & Medical Pharmacology
Affiliations
Member, Biochemistry, Biophysics & Structural Biology GPB Home Area, I3T Theme, JCCC Signal Transduction and Therapeutics Program Area, Molecular Pharmacology GPB Home Area, Molecular, Cellular & Integrative Physiology GPB Home Area
Research Interests
1. Longevity molecules that counteract aging and extend lifespan have long been a dream of humanity. Compared to ad libitum feeding, dietary restriction (DR) consistently extends lifespan and prevents age-related diseases. We discovered that a common metabolite, alpha-ketoglutarate (a-KG), acts as a direct molecular connection between dietary restriction and major aging regulatory proteins (Chin et al. 2014). Endogenous molecules such as a-KG that increase longevity suggest that an internal “fountain of youth” may exist that is accessible to interventions. Future research in this area offers enormous hopes and possibilities for better understanding of the molecular mechanisms of aging regulation, and for the prevention and treatment of age-related diseases, including major common killers such as cancer, heart disease, diabetes, and neurodegenerative diseases. 2. A second major area of interest in the lab is in technology and method development. Development of effective and safe therapies is the holy grail of medicine. For small-molecule drugs, a key challenge remains the identification of the molecular targets underlying drug therapeutic effects and/or adverse side effects. We have developed a simple, universally applicable target identification approach that analyzes direct drug binding to its target protein but does not require modification or immobilization of the small molecule (Lomenick et al. 2009). In this method, termed DARTS (drug affinity responsive target stability), small-molecule binding results in a pronounced and specific protection of its target protein from protease digestion. This specificity can be exploited to identify unknown binding targets of a small molecule with any cell lysate or protein mixture.
Publications
- Chai M, Jiang M, Vergnes L, Fu X, de Barros SC, Doan NB, Huang W, Chu J, Jiao J, Herschman H, Crooks GM, Reue K, Huang J. Stimulation of Hair Growth by Small Molecules that Activate Autophagy.. Cell reports, 2019.
- TeSlaa T, Chaikovsky AC, Lipchina I, Escobar SL, Hochedlinger K, Huang J, Graeber TG, Braas D, Teitell MA. α-Ketoglutarate Accelerates the Initial Differentiation of Primed Human Pluripotent Stem Cells.. Cell metabolism, 2016.
- Fu X, Chin RM, Vergnes L, Hwang H, Deng G, Xing Y, Pai MY, Li S, Ta L, Fazlollahi F, Chen C, Prins RM, Teitell MA, Nathanson DA, Lai A, Faull KF, Jiang M, Clarke SG, Cloughesy TF, Graeber TG, Braas D, Christofk HR, Jung ME, Reue K, Huang J. 2-Hydroxyglutarate Inhibits ATP Synthase and mTOR Signaling.. Cell metabolism, 2015.
- Lomenick B, Shi H, Huang J, Chen C. Identification and characterization of β-sitosterol target proteins.. Bioorganic & medicinal chemistry letters, 2015.
- Pai MY, Lomenick B, Hwang H, Schiestl R, McBride W, Loo JA, Huang J. Drug affinity responsive target stability (DARTS) for small-molecule target identification.. Methods in molecular biology (Clifton, N.J.), 2015.
- Chin RM, Fu X, Pai MY, Vergnes L, Hwang H, Deng G, Diep S, Lomenick B, Meli VS, Monsalve GC, Hu E, Whelan SA, Wang JX, Jung G, Solis GM, Fazlollahi F, Kaweeteerawat C, Quach A, Nili M, Krall AS, Godwin HA, Chang HR, Faull KF, Guo F, Jiang M, Trauger SA, Saghatelian A, Braas D, Christofk HR, Clarke CF, Teitell MA, Petrascheck M, Reue K, Jung ME, Frand AR, Huang J. The metabolite α-ketoglutarate extends lifespan by inhibiting ATP synthase and TOR.. Nature, 2014.
- Huang J. Tracking drugs.. The New England journal of medicine, 2013.
- Robinson TJ, Pai M, Liu JC, Vizeacoumar F, Sun T, Egan SE, Datti A, Huang J, Zacksenhaus E. High-throughput screen identifies disulfiram as a potential therapeutic for triple-negative breast cancer cells: interaction with IQ motif-containing factors.. Cell cycle (Georgetown, Tex.), 2013.
- Gao S, Wang Q, Wang G, Lomenick B, Liu J, Fan CW, Deng LW, Huang J, Lum L, Chen C. The Chemistry and Biology of Nakiterpiosin - C-nor-D-Homosteroids.. Synlett : accounts and rapid communications in synthetic organic chemistry, 2012.
- Lomenick B, Jung G, Wohlschlegel JA, Huang J. Target identification using drug affinity responsive target stability (DARTS).. Current protocols in chemical biology, 2011.
- Visnyei K, Onodera H, Damoiseaux R, Saigusa K, Petrosyan S, De Vries D, Ferrari D, Saxe J, Panosyan EH, Masterman-Smith M, Mottahedeh J, Bradley KA, Huang J, Sabatti C, Nakano I, Kornblum HI. A molecular screening approach to identify and characterize inhibitors of glioblastoma stem cells.. Molecular cancer therapeutics, 2011.
- Watanabe R, Wei L, Huang J. mTOR signaling, function, novel inhibitors, and therapeutic targets.. Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2011.
- Lomenick B, Olsen RW, Huang J. Identification of direct protein targets of small molecules.. ACS chemical biology, 2010.
- Aghajan M, Jonai N, Flick K, Fu F, Luo M, Cai X, Ouni I, Pierce N, Tang X, Lomenick B, Damoiseaux R, Hao R, Del Moral PM, Verma R, Li Y, Li C, Houk KN, Jung ME, Zheng N, Huang L, Deshaies RJ, Kaiser P, Huang J. Chemical genetics screen for enhancers of rapamycin identifies a specific inhibitor of an SCF family E3 ubiquitin ligase.. Nature biotechnology, 2010.
- Lomenick B, Hao R, Jonai N, Chin RM, Aghajan M, Warburton S, Wang J, Wu RP, Gomez F, Loo JA, Wohlschlegel JA, Vondriska TM, Pelletier J, Herschman HR, Clardy J, Clarke CF, Huang J. Target identification using drug affinity responsive target stability (DARTS).. Proceedings of the National Academy of Sciences of the United States of America, 2009.
- Saxe JP, Tomilin A, Schöler HR, Plath K, Huang J. Post-translational regulation of Oct4 transcriptional activity.. PloS one, 2009.
- Meng L, Michaud GA, Merkel JS, Zhou F, Huang J, Mattoon DR, Schweitzer B. Protein kinase substrate identification on functional protein arrays.. BMC biotechnology, 2008.
- Saxe JP, Wu H, Kelly TK, Phelps ME, Sun YE, Kornblum HI, Huang J. A phenotypic small-molecule screen identifies an orphan ligand-receptor pair that regulates neural stem cell differentiation.. Chemistry & biology, 2007.
- Sanchez AM, Thomas D, Gillespie EJ, Damoiseaux R, Rogers J, Saxe JP, Huang J, Manchester M, Bradley KA. Amiodarone and bepridil inhibit anthrax toxin entry into host cells.. Antimicrobial agents and chemotherapy, 2007.
- Jin F, Avramova L, Huang J, Hazbun T. A yeast two-hybrid smart-pool-array system for protein-interaction mapping.. Nature methods, 2007.
- Duncan MC, Ho DG, Huang J, Jung ME, Payne GS. Composite synthetic lethal identification of membrane traffic inhibitors.. Proceedings of the National Academy of Sciences of the United States of America, 2007.
- Kamata M, Wu RP, An DS, Saxe JP, Damoiseaux R, Phelps ME, Huang J, Chen IS. Cell-based chemical genetic screen identifies damnacanthal as an inhibitor of HIV-1 Vpr induced cell death.. Biochemical and biophysical research communications, 2006.
- Jin F, Hazbun T, Michaud GA, Salcius M, Predki PF, Fields S, Huang J. A pooling-deconvolution strategy for biological network elucidation.. Nature methods, 2006.
- Xie MW, Jin F, Hwang H, Hwang S, Anand V, Duncan MC, Huang J. Insights into TOR function and rapamycin response: chemical genomic profiling by using a high-density cell array method.. Proceedings of the National Academy of Sciences of the United States of America, 2005.
- Huang J, Zhu H, Haggarty SJ, Spring DR, Hwang H, Jin F, Snyder M, Schreiber SL. Finding new components of the target of rapamycin (TOR) signaling network through chemical genetics and proteome chips.. Proceedings of the National Academy of Sciences of the United States of America, 2004.
- Paulmurugan R, Massoud TF, Huang J, Gambhir SS. Molecular imaging of drug-modulated protein-protein interactions in living subjects.. Cancer research, 2004.
- Zewail A, Xie MW, Xing Y, Lin L, Zhang PF, Zou W, Saxe JP, Huang J. Novel functions of the phosphatidylinositol metabolic pathway discovered by a chemical genomics screen with wortmannin.. Proceedings of the National Academy of Sciences of the United States of America, 2003.
- Huang J, Weintraub H, Kedes L. Intramolecular regulation of MyoD activation domain conformation and function.. Molecular and cellular biology, 1998.
- Huang J, Schreiber SL. A yeast genetic system for selecting small molecule inhibitors of protein-protein interactions in nanodroplets.. Proceedings of the National Academy of Sciences of the United States of America, 1997.
- Sartorelli V, Huang J, Hamamori Y, Kedes L. Molecular mechanisms of myogenic coactivation by p300: direct interaction with the activation domain of MyoD and with the MADS box of MEF2C.. Molecular and cellular biology, 1997.
- Huang J, Blackwell TK, Kedes L, Weintraub H. Differences between MyoD DNA binding and activation site requirements revealed by functional random sequence selection.. Molecular and cellular biology, 1996.
- Blackwell TK, Huang J, Ma A, Kretzner L, Alt FW, Eisenman RN, Weintraub H. Binding of myc proteins to canonical and noncanonical DNA sequences.. Molecular and cellular biology, 1993.