Richard Goodman, M.D., Ph.D.

Richard H. Goodman, MD, PhD

Senior Scientist, Vollum Institute

Biography

Richard Goodman is a senior scientist in the Vollum Institute. He also holds appointments as professor of Cell, Developmental & Cancer Biology and Biochemistry and Molecular Biology. After receiving his B.S. degree in Chemistry at the Massachusetts Institute of Technology, he entered the Medical Scientist Training Program at the University of Pennsylvania. He received his M.D. and Ph.D. degrees in 1976. Goodman trained in clinical medicine at Tufts-New England Medical Center from 1976 to 1978 and was an endocrinology fellow at New England Medical Center and Massachusetts General Hospital. He was appointed as an assistant professor of Medicine at Harvard Medical School in 1982 and returned to Tufts-New England Medical Center in 1983, where he rose to the rank of professor of Medicine and chief of the Division of Molecular Medicine. He has been at the Vollum since 1990 and served as the Institute's director from 1990 until 2016.

Goodman's contributions include the characterization of the cAMP regulated enhancer (CRE), identification of the CREB coactivator, CBP, and one of the first genome-wide analyses of transcription factor binding sites in metazoan cells. Goodman is a member of the National Academy of Sciences, the Institute of Medicine, and served on the scientific review board of the Howard Hughes Medical Institute. He has trained 14 graduate students and 29 fellows, many of whom have gone on to have successful careers as independent investigators. His first student was recently elected into the National Academy of Sciences.

Summary of current research

The cAMP-regulated enhancer (CRE), initially identified in the Goodman lab, is a critical control element in many neuronal genes and the widespread presence of this element provides a mechanism that may allow coordinate regulation. Transcriptional signals mediated by the CRE depend upon the transcription factor CREB, which is activated through a variety of signaling pathways including cAMP, calcium, and growth factors. Phosphorylation of CREB leads to the recruitment of the CREB binding protein, CBP, which was also identified in the Goodman lab. CBP was the first example in metazoans of a transcriptional coactivator and has been shown to participate in virtually all positively regulated transcriptional pathways. Not surprisingly, perturbation of CBP function has profound effects on cell growth, differentiation, and development. One project in the lab uses laser microdissection and single cell RNASeq to identify genes in hippocampal granule cells that are induced by voluntary exercise. This study has identified a family of RNA transcripts that direct early steps in the formation of dendritic spines and current efforts (in collaboration with Gary Westbrook) are directed toward determining the contributions of the corresponding gene products to synaptic plasticity. A second project (in collaboration with Lulu Cambronne and Michael Cohen) is to elucidate the role of the nicotinamide adenine dinucleotide NAD+ in regulating cellular functions in health and disease. The ability of the biosensor developed in the lab to monitor free NAD+ levels in discrete subcellular compartments, which has never before been possible, will be important in sorting out the contribution of this molecule to neurodegeneration and the pathways connecting diet, gene regulation, and longevity.

Wolfe AD, Koberstein JN, Smith CB, Stewart ML, Gonzalez IJ, Hammarlund M, Hyman AA, Stork PJS, Goodman RH, Colón-Ramos DA. (2024) Local and dynamic regulation of neuronal glycolysis in vivo. Proc Natl Acad Sci U S A. 121(3):e2314699121.

Koberstein JN, Stewart ML, Smith CB, Tarasov AI, Ashcroft FM, Stork PJS, Goodman RH. (2022) Monitoring glycolytic dynamics in single cells using a fluorescent biosensor for fructose 1,6-bisphosphate. Proc Natl Acad Sci U S A. 119(31):e2204407119.

Chatzi C, Zhang G, Hendricks WD, Chen Y, Schnell E, Goodman RH*, Westbrook GL*. (2019) Exercise-induced enhancement of synaptic function triggered by the inverse BAR protein, Mtss1L. Elife 8:e45920. *co-senior authors

Liu HW, Smith CB, Schmidt MS, Cambronne XA, Cohen MS, Migaud ME, Brenner C, Goodman RH. (2018) Pharmacological bypass of NAD+ salvage pathway protects neurons from chemotherapy-induced degeneration. Proc. Natl. Acad. Sci. USA 115:10654-10659.

Mendoza-Viveros L, Chiang CK, Ong JLK, Hegazi S, Cheng AH, Bouchard-Cannon P, Fana M, Lowden C, Zhang P, Bothorel B, Michniewicz MG, Magill ST, Holmes MM, Goodman RH, Simonneaux V, Figeys D, Cheng HM. (2017) miR-132/212 modulates seasonal adaptation and dendritic morphology of the central circadian clock. Cell Rep. 19:505-520.

Cambronne XA, Stewart ML, Kim D, Jones-Brunette AM, Morgan RK, Farrens DL, Cohen MS, Goodman RH. (2016) Biosensor reveals multiple sources for mitochondrial NAD+. Science 352:1474-1477.

Barrett RM, Liu HW, Jin H, Goodman RH, Cohen MS. (2016) Cell-specific profiling of nascent proteomes using orthogonal enzyme-mediated puromycin incorporation. ACS Chem. Biol. 11pii: ENEURO.0024-16.2016.

Chatzi C, Zhang Y, Shen R, Westbrook GL, Goodman RH. (2016) Transcriptional profiling of newly generated dentate granule cells using TU tagging reveals pattern shifts in gene expression during circuit integration. eNeuro 3pii: ENEURO.0024-16.2016.

Thiebes KP, Nam H, Cambronne XA, Shen R, Glasgow SM, Cho HH, Kwon JS, Goodman RH, Lee JW, Lee S, Lee SK. (2015) miR-218 is essential to establish motor neuron fate as a downstream effector of Isl1-Lhx3. Nature Commun. 6:7718.

Hernandez-Rapp J, Smith PY, Filali M, Goupil C, Planel E, Magill ST, Goodman RH, Hébert SS. (2015) Memory formation and retention are affected in adult miR-132/212 knockout mice. Behav. Brain Res. 287:15-26.

Cambronne XA, Stewart ML, Kim D, Jones-Brunette AM, Morgan RK, Farrens DL, Cohen MS, Goodman RH. (2016) Biosensor reveals multiple sources for mitochondrial NAD+. Science 352:1474-1477.

Impey S, McCorkle SR, Cha-Molstad H, Dwyer JM, Yochum GS, Boss JM, McWeeney S, Dunn JJ, Mandel G, Goodman RH. (2004) Defining the CREB regulon: a genome-wide analysis of transcription factor regulatory regions. Cell 119:1041-1054.

Zhang Q, Piston DW, Goodman RH. (2002) Regulation of corepressor function by nuclear NADH. Science 295:1895-1897.

Goodman RH, Smolik S. (2000) CBP/p300 in cell growth, transformation, and development. Genes Dev. 14:1553-1577.

Kwok RP, Laurance ME, Lundblad JR, Goldman PS, Shih H, Connor LM, Marriott SJ, Goodman RH. (1996) Control of cAMP-regulated enhancers by the viral transactivator Tax through CREB and the co-activator CBP. Nature 380:642-646.

Lundblad JR, Kwok RP, Laurance ME, Harter ML, Goodman RH. (1995) Adenoviral ElA-associated protein p300 as a functional homologue of the transcriptional co-activator CBP. Nature 374:85-88.

Kwok RP, Lundblad JR, Chrivia JC, Richards JP, Bächinger HP, Brennan RG, Roberts SG, Green MR, Goodman RH. (1994) Nuclear protein CBP is a coactivator for the transcription factor CREB. Nature 370:223-226.

Chrivia JC, Kwok RP, Lamb N, Hagiwara M, Montminy MR, Goodman RH. (1993) Phosphorylated CREB binds specifically to the nuclear protein CBP. Nature 365:855-859.

Montminy MR, Sevarino KA, Wagner JA, Mandel G, Goodman RH. (1986) Identification of a cyclic-AMP-responsive element within the rat somatostatin gene. Proc. Natl. Acad. Sci. USA 83:6682-6686.

Lechan RM, Wu P, Jackson IM, Wolf H, Cooperman S, Mandel G, Goodman RH. (1986) Thyrotropin-releasing hormone precursor: characterization in rat brain. Science 231:159-161.