Biography

Download Curriculum Vitae

Dr. Rosenbaum earned his undergraduate degree in Chemistry from Princeton, where he carried out research in Michael Hecht's lab on the biophysical properties of de novo designed alpha helical proteins.

In his PhD work, Dr. Rosenbaum worked in the lab of David Liu in the Chemistry Department at Harvard, where he carried out directed evolution experiments to probe and alter protein-protein and protein-DNA interactions.

For his postdoc, Dr. Rosenbaum joined the lab of Brian Kobilka at Stanford University. Here he solved the crystal structure of the beta2 adrenergic receptor, the first atomic structure of a G protein coupled receptor (GPCR) activated by a diffusible ligand. He also helped to elucidate  conformational changes involved in beta2 receptor activation. These studies provided high-resolution molecular pictures of a GPCR bound to antagonist versus agonist, and set the stage for future structure determination of many biomedically important GPCRs.

Dr. Rosenbaum came to to UT Southwestern in the fall of 2010. His lab works on membrane protein signaling related to human disease. In continuing work on GPCRs, the Rosenbaum lab solved the first high-resolution structures of the orexin and cannabinoid receptors, physiologically important CNS GPCRs with great therapeutic signficance. The lab has also developed new labeling strategies for high-resolution NMR studies of wild type GPCRs, in order to probe the relationship between ligand efficacy and receptor dynamics. In ongoing work in the area of sterol homeostasis, the Rosenbaum lab solved the first crystal structure of a human sterol transporter, and is carrying out biophysical and biochemical studies on the mammalian sterol sensing machinery. The lab uses a variety of biophysical techniques, including X-ray crstallography, Cryo-electron microscopy, and NMR to investigate the structure-function relationships of these highly disease-relevant membrane proteins. Structural and mechanistic insights gained from this work are being used to pursue drug design against previously intractable targets.

Education

Undergraduate
Princeton University (1999), Chemistry
Graduate School
Harvard University (2005), Chemistry

Research Interest

  • G protein-coupled receptors
  • Membrane protein structural biology
  • Sterol/lipid homeostasis

Publications

Featured Publications LegendFeatured Publications

Direct Demonstration that Loop1 of Scap Binds to Loop7, a crucial event in cholesterol homeostasis.
Zhang Y, Lee KM, Kinch LN, Clark L, Grishin NV, Rosenbaum DM, Brown MS, Goldstein JL, Radhakrishnan A J. Biol. Chem. 2016 Apr
Methyl labeling and TROSY NMR spectroscopy of proteins expressed in the eukaryote Pichia pastoris.
Clark L, Zahm JA, Ali R, Kukula M, Bian L, Patrie SM, Gardner KH, Rosen MK, Rosenbaum DM J. Biomol. NMR 2015 May
Structure and dynamics of the M3 muscarinic acetylcholine receptor.
Kruse AC, Hu J, Pan AC, Arlow DH, Rosenbaum DM, Rosemond E, Green HF, Liu T, Chae PS, Dror RO, Shaw DE, Weis WI, Wess J, Kobilka BK Nature 2012 Feb 482 7386 552-6
Structure and function of an irreversible agonist-ß(2) adrenoceptor complex.
Rosenbaum DM, Zhang C, Lyons JA, Holl R, Aragao D, Arlow DH, Rasmussen SG, Choi HJ, Devree BT, Sunahara RK, Chae PS, Gellman SH, Dror RO, Shaw DE, Weis WI, Caffrey M, Gmeiner P, Kobilka BK Nature 2011 Jan 469 7329 236-40
Structure of a nanobody-stabilized active state of the ß(2) adrenoceptor.
Rasmussen SG, Choi HJ, Fung JJ, Pardon E, Casarosa P, Chae PS, Devree BT, Rosenbaum DM, Thian FS, Kobilka TS, Schnapp A, Konetzki I, Sunahara RK, Gellman SH, Pautsch A, Steyaert J, Weis WI, Kobilka BK Nature 2011 Jan 469 7329 175-80
Ligand-specific regulation of the extracellular surface of a G-protein-coupled receptor.
Bokoch MP, Zou Y, Rasmussen SG, Liu CW, Nygaard R, Rosenbaum DM, Fung JJ, Choi HJ, Thian FS, Kobilka TS, Puglisi JD, Weis WI, Pardo L, Prosser RS, Mueller L, Kobilka BK Nature 2010 Jan 463 7277 108-12
The structure and function of G-protein-coupled receptors.
Rosenbaum DM, Rasmussen SG, Kobilka BK Nature 2009 May 459 7245 356-63
Structure-based discovery of beta2-adrenergic receptor ligands.
Kolb P, Rosenbaum DM, Irwin JJ, Fung JJ, Kobilka BK, Shoichet BK Proc. Natl. Acad. Sci. U.S.A. 2009 Apr 106 16 6843-8
High-resolution crystal structure of an engineered human beta2-adrenergic G protein-coupled receptor.
Cherezov V, Rosenbaum DM, Hanson MA, Rasmussen SG, Thian FS, Kobilka TS, Choi HJ, Kuhn P, Weis WI, Kobilka BK, Stevens RC Science 2007 Nov 318 5854 1258-65
GPCR engineering yields high-resolution structural insights into beta2-adrenergic receptor function.
Rosenbaum DM, Cherezov V, Hanson MA, Rasmussen SG, Thian FS, Kobilka TS, Choi HJ, Yao XJ, Weis WI, Stevens RC, Kobilka BK Science 2007 Nov 318 5854 1266-73

Honors & Awards

  • Mallinckrodt Scholar
    (2017)
  • Amgen Young Investigator Award
    (2016)
  • Packard Fellow
    (2012)
  • Searle Scholar
    (2012)
  • UTSW Endowed Scholar
    (2010)
  • NIH NRSA Postdoctoral Fellowship
    (2007)