Harvard University - Department of Molecular & Cellular Biology

MEMBERS OF THE BOARD OF TUTORS

Liberles, Stephen, Ph.D.

Department of Cell Biology, Harvard Medical School

https://liberles.med.harvard.edu/

profile_image Molecular basis of instinctive animal behavior
Neural circuits that generate perception and control behavior are poorly understood at a molecular level. We are interested in understanding how the brain processes external sensory and internal homeostatic signals to initiate behavioral responses. First, we study olfactory cues, such as pheromones, food odors, and predator odors, that elicit innate mating, foraging, and avoidance responses in mice. Second, we are identifying hypothalamic genes that control feeding behavior and other instinctive drives.



(1) Pheromone signaling in mammals
Many social behaviors of the mouse, such as mating, fighting, and nurturing of young, involve the transmission and detection of pheromones. Sensory neurons in the mouse nose detect odors and pheromones using ~1,600 different G Protein-Coupled Receptors (GPCRs). We recently identified two novel families of mammalian olfactory receptors, termed trace amine-associated receptors (TAARs) and formyl peptide receptors (FPRs), some of which are prime candidates to detect semiochemicals such as pheromones and predator odors.



TAARs are olfactory receptors in diverse vertebrates- there are 15 in mice, 6 in human, and 113 in zebrafish. These receptors likely evolved from receptors for aminergic neurotransmitters and hormones that control behavior and emotion. Several TAAR ligands occur naturally in urine, a rich source of social odors for many mammals. The biosynthesis of some TAAR ligands is highly dynamic, varying with age, gender, or behavioral state. Furthermore, one TAAR ligand is a reported pheromone, raising the possibility that some TAARs are pheromone receptors that stimulate innate behaviors and physiological responses. We are studying all aspects of TAAR-mediated signaling, from the identity of natural product ligands to the characterization of neural pathways that influence behavior.

(2) Charting neural circuits that control appetite
The hypothalamus is an important regulator of instinctive behaviors- such as feeding, sleep, aggression, and sex. Studying the neural circuits that control these instinctive behaviors at a molecular level has presented a great challenge, in part because of limited technology. To study instinctive behaviors, we have developed a strategy of first purifying hypothalamic neurons that are activated during various behavioral states by flow cytometry, and then asking what genes they express by PCR.



Initial experiments have focused on characterizing neurons in the feeding control center of the hypothalamus, the arcuate nucleus. Specific neurons in the arcuate nucleus sense gut-derived feeding signals- such as insulin, leptin, and ghrelin- and respond by inducing a neural cascade that influences feeding behavior. We have been able to isolate hunger-activated neurons, and are beginning to search for novel genes expressed in these cells. In particular, we are focusing on cell surface receptors- such as GPCRs and tyrosine kinase receptors- that may serve as receptors for additional gut-derived signals. If the technique proves successful for identifying genes involved in appetite control, future projects will involve searching for genes that control other instinctive behaviors mediated by the hypothalamus.

next tutor: Lichtman, Jeff

Below is a listing of current tutors:

  • (1)   Aldovini, Anna , M.D., Division of Infectious Diseases, Children's Hospital
  • (2)   Auld, David , Ph.D., Department of Biology, Boston College
  • (3)   Ausubel, Frederick , Ph.D., Department of Molecular Biology, Massachusetts General Hospital
  • (4)   Berg, Howard , Ph.D., Department of Molecular and Cellular Biology, Harvard University
  • (5)   Brenner, Michael , Ph.D., Division of Engineering and Applied Sciences, Harvard University
  • (6)   Brenner, Tamara , Ph.D., Life Sciences Division, Harvard University
  • (7)   Buratowski, Stephen , Ph.D., BCMP, Harvard Medical School
  • (8)   Burton, Briana , Ph.D., Department of Molecular and Cellular Biology, Harvard University
  • (9)   Carroll, Michael , Ph.D., CBR Institute for Biomedical Research, Harvard Medical School
  • (10)   Chen, Bing , Ph.D., Laboratory of Molecular Medicine, Children's Hospital
  • (11)   Chou, James , Ph.D., BCMP, Harvard Medical School
  • (12)   Clapham, David , M.D., Ph.D., Department of Neurobiology, Children's Hospital
  • (13)   Clardy, John , Ph.D., BCMP, Harvard Medical School
  • (14)   D'Souza, Victoria , Ph.D., Department of Molecular and Cellular Biology, Harvard University
  • (15)   DePace, Angela , Ph.D., Department of Systems Biology, Harvard Medical School
  • (16)   Dulac, Catherine , Ph.D., Department of Molecular and Cellular Biology, Harvard University
  • (17)   Eck, Michael , M.D., Ph.D., BCMP, Dana-Farber Cancer Institute
  • (18)   Eggan, Kevin , Ph.D., Department of Molecular and Cellular Biology, Harvard University
  • (19)   Engert, Florian , Ph.D., Department of Molecular and Cellular Biology, Harvard University
  • (20)   Erikson, Raymond , Ph.D., Department of Molecular and Cellular Biology, Harvard University
  • (21)   Fisher, David , M.D., Ph.D., Department of Pediatrics, Dana Farber Cancer Institute
  • (22)   Fraenkel, Dan , Ph.D., Microbiology and Molecular Genetics, Harvard Medical School
  • (23)   Fraenkel, Ernest , Ph.D., Division of Biological Engineering, Massachusetts Institute of Technology
  • (24)   Fraenkel, Paula , M.D., Hematology/Oncology, Beth Israel Deaconess Medical Center
  • (25)   Gaudet, Rachelle , Ph.D., Department of Molecular and Cellular Biology, Harvard University
  • (26)   Goldfeld, Anne , M.D., CBR Institute for Biomedical Research, Harvard Medical School
  • (27)   Goldstein, Richard , Ph.D., Professor of Pediatrics, Boston Medical Center
  • (28)   Gray, Nathanael , Ph.D., BCMP, Harvard Medical School
  • (29)   Guidotti, Guido , M.D., Ph.D., Department of Molecular and Cellular Biology, Harvard University
  • (30)   Haigis, Marcia , Ph.D., Department of Pathology, Harvard Medical School
  • (31)   Harrison, Stephen , Ph.D., BCMP, Harvard Medical School
  • (32)   Hedley, Mary Lynne , Ph.D., MGI Pharma Biologics
  • (33)   Hinds, Philip , Ph.D., Molecular Oncology Research Institute, Tufts - New England Medical Center
  • (34)   Hung, Deborah , M.D., Ph.D., Microbiology and Molecular Genetics, Harvard Medical School
  • (35)   Hunter, Craig , Ph.D., Department of Molecular and Cellular Biology, Harvard University
  • (36)   Jasanoff, Alan , Ph.D., Nuclear Engineering/Brain & Cognitive Sciences, Massachusetts Institute of Technology
  • (37)   Kahne, Daniel , Ph.D., Department of Chemistry and Chemical Biology, Harvard University
  • (38)   Kay, Jeremy , Ph.D., Department of Molecular and Cellular Biology, Harvard University
  • (39)   Kieff, Elliott , M.D., Ph.D., Channing Laboratory, Brigham and Women's Hospital
  • (40)   Kirchhausen, Tomas , Ph.D., CBR Institute for Biomedical Research, Harvard Medical School
  • (41)   Kishony, Roy , Ph.D., Department of Systems Biology, Harvard Medical School
  • (42)   Kleckner, Nancy , Ph.D., Department of Molecular and Cellular Biology, Harvard University
  • (43)   Kolter, Roberto , Ph.D., Microbiology and Molecular Genetics, Harvard Medical School
  • (44)   Kopcow, Hernan , Ph.D., Department of Medicine, Beth Israel Deaconess Medical Center
  • (45)   Kunes, Samuel , Ph.D., Department of Molecular and Cellular Biology, Harvard University
  • (46)   Lahav, Galit , Ph.D., Department of Systems Biology, Harvard Medical School
  • (47)   Leschziner, Andres , Ph.D., Department of Molecular and Cellular Biology, Harvard University
  • (48)   Liberles, Stephen , Ph.D., Department of Cell Biology, Harvard Medical School
  • (49)   Lichtman, Jeff , M.D., Ph.D., Department of Molecular and Cellular Biology, Harvard University
  • (50)   Lieberman, Judy , M.D., Ph.D., CBR Institute for Biomedical Research, Harvard Medical School
  • (51)   Lilley, Brendan , Ph.D., Department of Molecular and Cellular Biology, Harvard University
  • (52)   Livingston, David , M.D., Department of Genetics, Dana-Farber Cancer Institute
  • (53)   Loeken, Mary , Ph.D., Developmental and Stem Cell Biology, Joslin Diabetes Center, Harvard Medical School
  • (54)   Losick, Richard , Ph.D., Department of Molecular and Cellular Biology, Harvard University
  • (55)   Lue, Robert , Ph.D., Department of Molecular and Cellular Biology, Harvard University
  • (56)   Magasanik, Boris , Ph.D., Biology Department, Massachusetts Institute of Technology
  • (57)   McKeon, Frank , Ph.D., Department of Cell Biology, Harvard Medical School
  • (58)   Michel, Thomas , M.D., Ph.D., Cardiovascular Division, Brigham and Women's Hospital
  • (59)   Miller, Jeffrey , Ph.D., Neuromuscular Biology & Disease Group, Boston Biomedical Research Institute
  • (60)   Miller, Theodore , Ph.D., Chief Executive Officer, Reify Corporation
  • (61)   Moazed, Danesh , Ph.D., Department of Cell Biology, Harvard Medical School
  • (62)   Murthy, Venkatesh , Ph.D., Department of Molecular and Cellular Biology, Harvard University
  • (63)   Navia, Manuel , , Oxford Bioscience Partners
  • (64)   Nelson, David , Ph.D., Department of Physics, Harvard University
  • (65)   Olesen, James , Ph.D., Wilmer Cutler Pickering Hale and Door LLP
  • (66)   Peattie, Debra , MBA, Ph.D., Harvard University
  • (67)   Ranjbar, Shahin , Ph.D., Children's Hospital, Harvard Medical School
  • (68)   Rheinwald, James , Ph.D., Department of Dermatology, Brigham and Women's Hospital
  • (69)   Rivera-Feliciano, Jose , Ph.D., Stem Cell and Regenerative Biology, Harvard University
  • (70)   Sabeti, Pardis , D.Phil, M.D., FAS Center for Systems Biology, Harvard University
  • (71)   Sanes, Joshua , Ph.D., Department of Molecular and Cellular Biology, Harvard University
  • (72)   Sassanfar, Mandana , Ph.D., Department of Biology, Massachusetts Institute of Technology
  • (73)   Sato, Vicki , Ph.D., Technology and Operations Management, Harvard Business School
  • (74)   Schier, Alexander , Ph.D., Department of Molecular and Cellular Biology, Harvard University
  • (75)   Shamu, Caroline , Ph.D., Department of Systems Biology, Harvard Medical School
  • (76)   Shi, Yang , Ph.D., Department of Pathology, Harvard Medical School
  • (77)   Silberstein, Lev , M.D., Ph.D., Harvard University
  • (78)   Starnbach, Michael , Ph.D., Microbiology and Molecular Genetics, Harvard Medical School
  • (79)   Stern, Bodo , Ph.D., FAS Center for Systems Biology, Harvard University
  • (80)   Stern, Joel N.H. , Ph.D., Department of Molecular and Cellular Biology, Harvard University
  • (81)   Strominger, Jack , Ph.D., Department of Molecular and Cellular Biology, Harvard University
  • (82)   Sweadner, Kathleen , M.D., Harvard University
  • (83)   Tong, Jeffrey , Ph.D., Nora Therapeutics
  • (84)   Torello, A. Thomas , Ph.D., Department of Molecular and Cellular Biology, Harvard University
  • (85)   Toth, Joseph , Ph.D., Merrimack Pharmaceuticals
  • (86)   Tucci, Greg , Ph.D., Department of Chemistry and Chemical Biology, Harvard University
  • (87)   Vaughan, Cheryl , Ph.D., Graduate Program in Biotechnology, Harvard University
  • (88)   Viel, Alain , Ph.D., Department of Molecular and Cellular Biology, Harvard University
  • (89)   Walker, Suzanne , Ph.D., Microbiology and Molecular Genetics, Harvard Medical School
  • (90)   Winston, Fred , Ph.D., Department of Genetics, Harvard Medical School