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/).
TGF-beta signaling is required for multiple processes during Xenopus tail regeneration. Dev Biol. 2008 Mar 01; 315(1):203-16.
TGF-beta signaling is required for multiple processes during Xenopus tail regeneration.
Nodal signaling in early vertebrate embryos: themes and variations. Dev Cell. 2001 Nov; 1(5):605-17.
Nodal signaling in early vertebrate embryos: themes and variations.
Novel Nutrient-sensing Pathway Suppresses Pathologic Tissue Remodeling
John Franklin Enders University Professor of Systems Biology
Instructor in Developmental Biology, Part-time
Corresponding Member of the Faculty of Restorative Dentistry and Biomaterials Sciences
George Jacob and Jacqueline Hazel Leder Professor of Genetics
Doctors Samuel and Ida Gelfand Professor of Developmental Biology
Professor of Stem Cell and Regenerative Biology and Grousbeck Professor of Pediatrics, Harvard Medical School
James Stillman Professor of Developmental Biology
Kim Y, Sundrud MS, Zhou C, Edenius M, Zocco D, Powers K, Zhang M, Mazitschek R, Rao A, Yeo CY, Noss EH, Brenner MB, Whitman M, Keller TL
Proceedings of the National Academy of Sciences of the United States of America
Aminoacyl-tRNA synthetase inhibition activates a pathway that branches from the canonical amino acid response in mammalian cells. Proc Natl Acad Sci U S A. 2020 04 21; 117(16):8900-8911.
Aminoacyl-tRNA synthetase inhibition activates a pathway that branches from the canonical amino acid response in mammalian cells.
Revollo L, Merrill-Skoloff G, De Ceunynck K, Dilks JR, Guo S, Bordoli MR, Peters CG, Noetzli L, Ionescu A, Rosen V, Italiano JE, Whitman M, Flaumenhaft R
The secreted tyrosine kinase VLK is essential for normal platelet activation and thrombus formation. Blood. 2022 01 06; 139(1):104-117.
The secreted tyrosine kinase VLK is essential for normal platelet activation and thrombus formation.
Maridas DE, Gamer L, Moore ER, Doedens AM, Yu Y, Ionescu A, Revollo L, Whitman M, Rosen V
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
Loss of Vlk in Prx1+ Cells Delays the Initial Steps of Endochondral Bone Formation and Fracture Repair in the Limb. J Bone Miner Res. 2022 04; 37(4):764-775.
Loss of Vlk in Prx1+ Cells Delays the Initial Steps of Endochondral Bone Formation and Fracture Repair in the Limb.
Tye MA, Payne NC, Johansson C, Singh K, Santos SA, Fagbami L, Pant A, Sylvester K, Luth MR, Marques S, Whitman M, Mota MM, Winzeler EA, Lukens AK, Derbyshire ER, Oppermann U, Wirth DF, Mazitschek R
Elucidating the path to Plasmodium prolyl-tRNA synthetase inhibitors that overcome halofuginone resistance. Nat Commun. 2022 08 25; 13(1):4976.
Elucidating the path to Plasmodium prolyl-tRNA synthetase inhibitors that overcome halofuginone resistance.
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.
Regarding the mechanism of action of a proposed peptide agonist of the bone morphogenetic protein receptor activin-like kinase 3.
Dental Health Care for Special Needs Individuals: Trinidad and Tobago Summer Camp Case Study
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
American journal of medical genetics. Part A
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.
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.
Teaching Associate in Obstetrics, Gynecology and Reproductive Biology
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):1033-1044.
A secreted tyrosine kinase acts in the extracellular environment.
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.
The cytoplasmic prolyl-tRNA synthetase of the malaria parasite is a dual-stage target of febrifugine and its analogs.
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.
Evidence for cadherin-11 cleavage in the synovium and partial characterization of its mechanism.
Menthol Cigarettes and Tobacco Dependence in Elderly Nursing Home Residents
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
The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation
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.
Halofuginone treatment reduces interleukin-17A and ameliorates features of chronic lung allograft dysfunction in a mouse orthotopic lung transplant model.
Breast Cancer Bone Metastasis: RANKL signalling and MMP-2 mediated invasion
Regulation of Xenopus Embryonic Development by TGFbeta Superfamily Ligands and SM
SIGNAL TRANSDUCTION IN VERTEBRATE EMBRYO DEVELOPMENT
Role of the first secreted tyrosine kinase in bone development, homeostasis, and repair.
MECHANISM OF ACTION OF HALOFUGINONE AS A NOVEL THERAPEUTIC
Role of a Novel Secreted Protein Tyrosine Kinase in Development
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 01; 16(21):2749-54.
Activin type IIA and IIB receptors mediate Gdf11 signaling in axial vertebral patterning.
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 05; 324(5932):1334-8.
Halofuginone inhibits TH17 cell differentiation by activating the amino acid starvation response.
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.
Mixer/Bon and FoxH1/Sur have overlapping and divergent roles in Nodal signaling and mesendoderm induction.
Watanabe M, Rebbert ML, Andreazzoli M, Takahashi N, Toyama R, Zimmerman S, Whitman M, Dawid IB
Developmental dynamics : an official publication of the American Association of Anatomists
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.
Regulation of the Lim-1 gene is mediated through conserved FAST-1/FoxH1 sites in the first intron.
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.
Xnr2 and Xnr5 unprocessed proteins inhibit Wnt signaling upstream of dishevelled.
Inhibitor-resistant type I receptors reveal specific requirements for TGF-beta signaling in vivo. Dev Biol. 2006 Jul 15; 295(2):730-42.
Inhibitor-resistant type I receptors reveal specific requirements for TGF-beta signaling in vivo.
Nodal signals to Smads through Cripto-dependent and Cripto-independent mechanisms. Mol Cell. 2001 May; 7(5):949-57.
Nodal signals to Smads through Cripto-dependent and Cripto-independent mechanisms.
Faure S, de Santa Barbara P, Roberts DJ, Whitman M
Endogenous patterns of BMP signaling during early chick development. Dev Biol. 2002 Apr 01; 244(1):44-65.
Endogenous patterns of BMP signaling during early chick development.
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.
New roles for FoxH1 in patterning the early embryo.
p53 and TGF-beta in development: prelude to tumor suppression? Cell. 2003 May 02; 113(3):275-6.
p53 and TGF-beta in development: prelude to tumor suppression?
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.
A Serpin family gene, protease nexin-1 has an activity distinct from protease inhibition in early Xenopus embryos.
TGFbeta signaling at the summit. Development. 2005 Oct; 132(19):4205-10.
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.
Small ubiquitin-like modifier (SUMO) modification mediates function of the inhibitory domains of developmental regulators FOXC1 and FOXC2.
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.
Microarray profiling reveals the integrated stress response is activated by halofuginone in mammary epithelial cells.
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 04; 389(6646):85-9.
Smad4 and FAST-1 in the assembly of activin-responsive factor.
Smads and early developmental signaling by the TGFbeta superfamily. Genes Dev. 1998 Aug 15; 12(16):2445-62.
Smads and early developmental signaling by the TGFbeta superfamily.
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.
XCR2, one of three Xenopus EGF-CFC genes, has a distinct role in the regulation of left-right patterning.
Identification of a novel pool of extracellular pro-myostatin in skeletal muscle. J Biol Chem. 2008 Mar 14; 283(11):7027-35.
Identification of a novel pool of extracellular pro-myostatin in skeletal muscle.
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.
Halofuginone and other febrifugine derivatives inhibit prolyl-tRNA synthetase.
A transcriptional partner for MAD proteins in TGF-beta signalling. Nature. 1996 Oct 24; 383(6602):691-6.
A transcriptional partner for MAD proteins in TGF-beta signalling.
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.
TRIQK, a novel family of small proteins localized to the endoplasmic reticulum membrane, is conserved across vertebrates.
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.
The role and regulation of GDF11 in Smad2 activation during tailbud formation in the Xenopus embryo.
Oxidative stress drives disulfide bond formation between basic helix-loop-helix transcription factors. J Cell Biochem. 2010 Feb 01; 109(2):417-24.
Oxidative stress drives disulfide bond formation between basic helix-loop-helix transcription factors.
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.
Conditional BMP inhibition in Xenopus reveals stage-specific roles for BMPs in neural and neural crest induction.