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profileMalcolm Russell Whitman, Ph.D.

TitleProfessor of Developmental Biology
InstitutionHarvard School of Dental Medicine
DepartmentDevelopmental Biology
AddressHarvard School of Dental Medicine
Developmental Biology REB 505
188 Longwood Ave
Boston MA 02115
Phone617/432-1320
Fax617/432-5747
vCardDownload vCard (login for email)

Collapse Overview 
Collapse overview
Malcolm Whitman received his undergraduate degree in Biology from Yale College and his PhD from the Biochemistry and Molecular Biology Department at Harvard University. His thesis work in the lab of Lew Cantley investigated the association of phosphatidylinositol kinases with oncogene and growth factor receptor tyrosine kinases, and culminated in the discovery of the phosphatidylinositol-3-kinase signal transduction pathway. In his postdoctoral work with Doug Melton, he developed the frog embryo as a tool for studying mechanisms of growth factor signaling during early development.

As an independent investigator, Dr. Whitman has focused on transduction of TGFß superfamily signals. The laboratory identified the first Smad-interacting transcription factor, FAST-1, and established that FAST-1 has a central role in the regulation of early developmental patterning by TGFß ligands. His current research interests continue to address the problem of how TGFß superfamily ligands signal in different contexts, and how TGFß signaling might be manipulated in vivo for therapeutic purposes.

The Whitman laboratory is also interested in how metabolic sensors regulate chronic inflammatory disease. The lab has recently established that a natural product derived small molecule, halofuginone, exerts anti-inflammatory effects by mimicking a lack of amino acid availability, thereby activating a metabolic sensor pathway known as the amino acid response.

Dr. Whitman is a Professor of Developmental Biology at the Harvard School of Dental Medicine and an affiliate member of the Department of Cell Biology at Harvard Medical School. He is a member of the BBS graduate program (http://www.hms.harvard.edu/dms/bbs/), an affiliate of the Harvard Stem Cell Institute (http://www.hsci.harvard.edu/) the Dana Farber/Harvard Cancer Center Cancer Cell Biology Program (http://www.dfhcc.harvard.edu/research-programs/discipline-based-programs/cancer-cell-biology/ ) and a member of the executive committee for the Harvard Developmental and Regenerative Biology program (https://drb.hms.harvard.edu/).


Collapse Mentoring 
Collapse completed student projects
Dental Health Care for Special Needs Individuals: Trinidad and Tobago Summer Camp Case Study
International/Summer, 06/24/13 - 07/27/13
Menthol Cigarettes and Tobacco Dependence in Elderly Nursing Home Residents
Summer, 06/14/10 - 08/13/10
Breast Cancer Bone Metastasis: RANKL signalling and MMP-2 mediated invasion
Summer, 06/11/07 - 08/17/07

Collapse Research 
Collapse research activities and funding
The research activities and funding listed below are automatically derived from NIH ExPORTER and other sources, which might result in incorrect or missing items. Faculty can login to make corrections and additions.
R01GM115417     (WHITMAN, MALCOLM R.)Sep 17, 2015 - Aug 31, 2019
NIH/NIGMS
The first secreted Tyrosine kinase
Role: Principal Investigator

R01AR066717     (ROSEN, VICKI)Apr 1, 2015 - Mar 31, 2020
NIH/NIAMS
Role of the first secreted tyrosine kinase in bone development, homeostasis, and repair.
Role: Co-Principal Investigator

R21DE024312     (WHITMAN, MALCOLM R.)Apr 9, 2014 - Mar 31, 2016
NIH/NIDCR
Role of a Novel Secreted Protein Tyrosine Kinase in Development
Role: Principal Investigator

R01GM089885     (WHITMAN, MALCOLM R.)Apr 1, 2010 - Feb 28, 2014
NIH/NIGMS
MECHANISM OF ACTION OF HALOFUGINONE AS A NOVEL THERAPEUTIC
Role: Principal Investigator

R01HD029468     (WHITMAN, MALCOLM R.)Aug 5, 1992 - Aug 31, 2012
NIH/NICHD
Regulation of Xenopus Embryonic Development by TGFbeta Superfamily Ligands and SM
Role: Principal Investigator

Collapse Bibliographic 
Collapse selected publications
Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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  1. Oishi H, Martinu T, Sato M, Matsuda Y, Hirayama S, Juvet SC, Guan Z, Saito T, Cypel M, Hwang DM, Keller TL, Whitman MR, Liu M, Keshavjee S. Halofuginone treatment reduces interleukin-17A and ameliorates features of chronic lung allograft dysfunction in a mouse orthotopic lung transplant model. J Heart Lung Transplant. 2016 Apr; 35(4):518-27. PMID: 26787621.
    View in: PubMed
  2. Herman JD, Pepper LR, Cortese JF, Estiu G, Galinsky K, Zuzarte-Luis V, Derbyshire ER, Ribacke U, Lukens AK, Santos SA, Patel V, Clish CB, Sullivan WJ, Zhou H, Bopp SE, Schimmel P, Lindquist S, Clardy J, Mota MM, Keller TL, Whitman M, Wiest O, Wirth DF, Mazitschek R. The cytoplasmic prolyl-tRNA synthetase of the malaria parasite is a dual-stage target of febrifugine and its analogs. Sci Transl Med. 2015 May 20; 7(288):288ra77. PMID: 25995223.
    View in: PubMed
  3. Noss EH, Watts GF, Zocco D, Keller TL, Whitman M, Blobel CP, Lee DM, Brenner MB. Evidence for cadherin-11 cleavage in the synovium and partial characterization of its mechanism. Arthritis Res Ther. 2015 May 15; 17:126. PMID: 25975695; PMCID: PMC4449585.
  4. Bordoli MR, Yum J, Breitkopf SB, Thon JN, Italiano JE, Xiao J, Worby C, Wong SK, Lin G, Edenius M, Keller TL, Asara JM, Dixon JE, Yeo CY, Whitman M. A secreted tyrosine kinase acts in the extracellular environment. Cell. 2014 Aug 28; 158(5):1033-44. PMID: 25171405; PMCID: PMC4149754.
  5. Rienhoff HY, Yeo CY, Morissette R, Khrebtukova I, Melnick J, Luo S, Leng N, Kim YJ, Schroth G, Westwick J, Vogel H, McDonnell N, Hall JG, Whitman M. A mutation in TGFB3 associated with a syndrome of low muscle mass, growth retardation, distal arthrogryposis and clinical features overlapping with Marfan and Loeys-Dietz syndrome. Am J Med Genet A. 2013 Aug; 161A(8):2040-6. PMID: 23824657; PMCID: PMC3885154.
  6. Whitman M, Rosen V, Brivanlou AH, Groppe JC, Sebald W, Mueller T. Regarding the mechanism of action of a proposed peptide agonist of the bone morphogenetic protein receptor activin-like kinase 3. Nat Med. 2013 Jul; 19(7):809-10. PMID: 23836213.
    View in: PubMed
  7. Keller TL, Zocco D, Sundrud MS, Hendrick M, Edenius M, Yum J, Kim YJ, Lee HK, Cortese JF, Wirth DF, Dignam JD, Rao A, Yeo CY, Mazitschek R, Whitman M. Halofuginone and other febrifugine derivatives inhibit prolyl-tRNA synthetase. Nat Chem Biol. 2012 Feb 12; 8(3):311-7. PMID: 22327401; PMCID: PMC3281520.
  8. Kamberov YG, Kim J, Mazitschek R, Kuo WP, Whitman M. Microarray profiling reveals the integrated stress response is activated by halofuginone in mammary epithelial cells. BMC Res Notes. 2011 Oct 05; 4:381. PMID: 21974968; PMCID: PMC3197508.
  9. Onuma Y, Watanabe A, Aburatani H, Asashima M, Whitman M. TRIQK, a novel family of small proteins localized to the endoplasmic reticulum membrane, is conserved across vertebrates. Zoolog Sci. 2008 Jul; 25(7):706-13. PMID: 18828657.
    View in: PubMed
  10. Anderson SB, Goldberg AL, Whitman M. Identification of a novel pool of extracellular pro-myostatin in skeletal muscle. J Biol Chem. 2008 Mar 14; 283(11):7027-35. PMID: 18175804.
    View in: PubMed
  11. Ho DM, Chan J, Bayliss P, Whitman M. Inhibitor-resistant type I receptors reveal specific requirements for TGF-beta signaling in vivo. Dev Biol. 2006 Jul 15; 295(2):730-42. PMID: 16684517.
    View in: PubMed
  12. Onuma Y, Asashima M, Whitman M. A Serpin family gene, protease nexin-1 has an activity distinct from protease inhibition in early Xenopus embryos. Mech Dev. 2006 Jun; 123(6):463-71. PMID: 16797167.
    View in: PubMed
  13. Onuma Y, Yeo CY, Whitman M. XCR2, one of three Xenopus EGF-CFC genes, has a distinct role in the regulation of left-right patterning. Development. 2006 Jan; 133(2):237-50. PMID: 16339189.
    View in: PubMed
  14. Whitman M, Raftery L. TGFbeta signaling at the summit. Development. 2005 Oct; 132(19):4205-10. PMID: 16155212.
    View in: PubMed
  15. Wawersik S, Evola C, Whitman M. Conditional BMP inhibition in Xenopus reveals stage-specific roles for BMPs in neural and neural crest induction. Dev Biol. 2005 Jan 15; 277(2):425-42. PMID: 15617685.
    View in: PubMed
  16. Kofron M, Puck H, Standley H, Wylie C, Old R, Whitman M, Heasman J. New roles for FoxH1 in patterning the early embryo. Development. 2004 Oct; 131(20):5065-78. PMID: 15459100.
    View in: PubMed
  17. Kunwar PS, Zimmerman S, Bennett JT, Chen Y, Whitman M, Schier AF. Mixer/Bon and FoxH1/Sur have overlapping and divergent roles in Nodal signaling and mesendoderm induction. Development. 2003 Dec; 130(23):5589-99. PMID: 14522874.
    View in: PubMed
  18. Whitman M, McKeon F. p53 and TGF-beta in development: prelude to tumor suppression? Cell. 2003 May 2; 113(3):275-6. PMID: 12732134.
    View in: PubMed
  19. Watanabe M, Rebbert ML, Andreazzoli M, Takahashi N, Toyama R, Zimmerman S, Whitman M, Dawid IB. Regulation of the Lim-1 gene is mediated through conserved FAST-1/FoxH1 sites in the first intron. Dev Dyn. 2002 Dec; 225(4):448-56. PMID: 12454922.
    View in: PubMed
  20. Oh SP, Yeo CY, Lee Y, Schrewe H, Whitman M, Li E. Activin type IIA and IIB receptors mediate Gdf11 signaling in axial vertebral patterning. Genes Dev. 2002 Nov 1; 16(21):2749-54. PMID: 12414726; PMCID: PMC187472.
  21. Faure S, de Santa Barbara P, Roberts DJ, Whitman M. Endogenous patterns of BMP signaling during early chick development. Dev Biol. 2002 Apr 1; 244(1):44-65. PMID: 11900458.
    View in: PubMed
  22. Whitman M. Nodal signaling in early vertebrate embryos: themes and variations. Dev Cell. 2001 Nov; 1(5):605-17. PMID: 11709181.
    View in: PubMed
  23. Yeo C, Whitman M. Nodal signals to Smads through Cripto-dependent and Cripto-independent mechanisms. Mol Cell. 2001 May; 7(5):949-57. PMID: 11389842.
    View in: PubMed
  24. Whitman M. Smads and early developmental signaling by the TGFbeta superfamily. Genes Dev. 1998 Aug 15; 12(16):2445-62. PMID: 9716398.
    View in: PubMed
  25. Chen X, Weisberg E, Fridmacher V, Watanabe M, Naco G, Whitman M. Smad4 and FAST-1 in the assembly of activin-responsive factor. Nature. 1997 Sep 4; 389(6646):85-9. PMID: 9288972.
    View in: PubMed
  26. Chen X, Rubock MJ, Whitman M. A transcriptional partner for MAD proteins in TGF-beta signalling. Nature. 1996 Oct 24; 383(6602):691-6. PMID: 8878477.
    View in: PubMed
  27. Ho DM, Yeo CY, Whitman M. The role and regulation of GDF11 in Smad2 activation during tailbud formation in the Xenopus embryo. Mech Dev. 2010 Sep-Dec; 127(9-12):485-95. PMID: 20807570; PMCID: PMC4136463.
  28. Onuma Y, Takahashi S, Haramoto Y, Tanegashima K, Yokota C, Whitman M, Asashima M. Xnr2 and Xnr5 unprocessed proteins inhibit Wnt signaling upstream of dishevelled. Dev Dyn. 2005 Dec; 234(4):900-10. PMID: 16193491.
    View in: PubMed
  29. Sundrud MS, Koralov SB, Feuerer M, Calado DP, Kozhaya AE, Rhule-Smith A, Lefebvre RE, Unutmaz D, Mazitschek R, Waldner H, Whitman M, Keller T, Rao A. Halofuginone inhibits TH17 cell differentiation by activating the amino acid starvation response. Science. 2009 Jun 5; 324(5932):1334-8. PMID: 19498172; PMCID: PMC2803727.
  30. Danciu TE, Chupreta S, Cruz O, Fox JE, Whitman M, Iñiguez-Lluhí JA. Small ubiquitin-like modifier (SUMO) modification mediates function of the inhibitory domains of developmental regulators FOXC1 and FOXC2. J Biol Chem. 2012 May 25; 287(22):18318-29. PMID: 22493429; PMCID: PMC3365760.
  31. Ho DM, Whitman M. TGF-beta signaling is required for multiple processes during Xenopus tail regeneration. Dev Biol. 2008 Mar 1; 315(1):203-16. PMID: 18234181; PMCID: PMC2292344.
  32. Danciu TE, Whitman M. Oxidative stress drives disulfide bond formation between basic helix-loop-helix transcription factors. J Cell Biochem. 2010 Feb 1; 109(2):417-24. PMID: 19950203.
    View in: PubMed
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