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.
- Princeton University (1999), Chemistry
- Graduate School
- Harvard University (2005), Chemistry
- G protein-coupled receptors
- Membrane protein structural biology
- Sterol/lipid homeostasis
- Structure of an allosteric modulator bound to the CB1 cannabinoid receptor.
- Shao Z, Yan W, Chapman K, Ramesh K, Ferrell AJ, Yin J, Wang X, Xu Q, Rosenbaum DM, Nat. Chem. Biol. 2019 12 15 12 1199-1205
- Ligand modulation of sidechain dynamics in a wild-type human GPCR.
- Clark LD, Dikiy I, Chapman K, Rödström KE, Aramini J, LeVine MV, Khelashvili G, Rasmussen SG, Gardner KH, Rosenbaum DM Elife 2017 Oct 6
- High-resolution crystal structure of the human CB1 cannabinoid receptor.
- Shao Z, Yin J, Chapman K, Grzemska M, Clark L, Wang J, Rosenbaum DM Nature 2016 Nov
- Crystal structure of the human sterol transporter ABCG5/ABCG8.
- Lee JY, Kinch LN, Borek DM, Wang J, Wang J, Urbatsch IL, Xie XS, Grishin NV, Cohen JC, Otwinowski Z, Hobbs HH, Rosenbaum DM Nature 2016 May 533 7604 561-4
- Structure and ligand-binding mechanism of the human OX1 and OX2 orexin receptors.
- Yin J, Babaoglu K, Brautigam CA, Clark L, Shao Z, Scheuermann TH, Harrell CM, Gotter AL, Roecker AJ, Winrow CJ, Renger JJ, Coleman PJ, Rosenbaum DM Nat. Struct. Mol. Biol. 2016 Mar
- Crystal structure of the human OX2 orexin receptor bound to the insomnia drug suvorexant.
- Yin J, Mobarec JC, Kolb P, Rosenbaum DM Nature 2014 Dec
- Isotopic Labeling of Eukaryotic Membrane Proteins for NMR Studies of Interactions and Dynamics.
- Dikiy I, Clark LD, Gardner KH, Rosenbaum DM Meth. Enzymol. 2019 614 37-65
- tachykinin receptor.
- Yin J, Chapman K, Clark LD, Shao Z, Borek D, Xu Q, Wang J, Rosenbaum DM Proc. Natl. Acad. Sci. U.S.A. 2018 Dec 115 52 13264-13269
- Crystal Structures of Human Orexin 2 Receptor Bound to the Subtype-Selective Antagonist EMPA.
- Suno R, Kimura KT, Nakane T, Yamashita K, Wang J, Fujiwara T, Yamanaka Y, Im D, Horita S, Tsujimoto H, Tawaramoto MS, Hirokawa T, Nango E, Tono K, Kameshima T, Hatsui T, Joti Y, Yabashi M, Shimamoto K, Yamamoto M, Rosenbaum DM, Iwata S, Shimamura T, Kobayashi T Structure 2017 Nov
- The Human Orexin/Hypocretin Receptor Crystal Structures.
- Yin J, Rosenbaum DM Curr Top Behav Neurosci 2016 Dec
Honors & Awards
- Mallinckrodt Scholar
- Amgen Young Investigator Award
- Packard Fellow
- Searle Scholar
- UTSW Endowed Scholar
- NIH NRSA Postdoctoral Fellowship