Georgia E. Hodes

My goal is to identify biological mechanisms that contribute to individual differences in vulnerability and resilience to stress and mood disorders such as anxiety and depression. In particular, I am interested in understanding how the sex of an individual contributes to stress susceptibility. I want to develop novel personalized treatments and bioassays for mental illness so these disorders can be medically diagnosed and treated effectively.

My initial education was in the liberal arts. I received a B.A. in Drama/Dance from Bard College and worked as an actor and a designer in New York City. I eventually went back to school and obtained post-baccalaureate training at Hunter College in order to pursue a graduate degree in Neuroscience. I went on to obtain a Ph.D. from Rutgers University in the Behavioral and Systems Neuroscience division of the Psychology program. At Rutgers, I trained with Dr. Tracey Shors exploring sex differences in the effects of stress on cognition and brain plasticity across the lifespan. In 2007 I began postdoctoral training in Pharmacology with Dr. Irwin Lucki at the University of Pennsylvania examining the contribution of adult neurogenesis and neurotrophin mobilization to genetic and sex differences in vulnerability to stress. In 2010, I joined the laboratory of Dr. Scott Russo as a post-doctoral fellow for training in molecular neuroscience. My work at Mt. Sinai focused on neuro-immunological and epigenetic mechanisms contributing to individual differences in stress susceptibility. In 2013 I received a NARSAD young investigator award to examine the role of the cytokine Interleukin-6 in stress susceptibility. In 2015 I was promoted to Assistant Professor at Mt. Sinai. I am honored and excited to join the faculty of VT in 2016. My research program examines sex differences in the peripheral and central immune system and how immune mechanisms interact with brain plasticity to drive behavioral differences in susceptibility and resiliency to stress. My research interests include examining the molecular substrates directing the functional contribution of hormones and cytokines to the onset, symptoms, and generational transmission of mood disorders in both sexes.

Hodes laboratory: The contribution of sex specific immune interactions with the brain to mood disorders.

Mood disorders such as depression and anxiety are debilitating and are a growing disability throughout the world. Currently available antidepressant treatments are all based on a similar biochemical mechanism and are effective in only 50% of the population. Furthermore, most current medications were developed via a preclinical stage that only used in male subjects, even though females have twice the occurrence of mood disorders. Given the heterogeneous nature of mood disorders it is unlikely that a one treatment will help all. Therefore, there is a genuine need to develop novel personalized diagnostics and treatments so that mental disorders can be diagnosed medically and treated effectively.

Planned projects

  • Sex differences in the peripheral immune system functionally contribute to stress susceptibility and resilience.

These studies will determine the peripheral cellular signatures of depression in both sexes. By comparing these signatures with a mouse model we can explore which signatures actively contribute to stress susceptibility and resilience and which are selectively important for females vs. males. This will inform how stress alters the ability of immune cells to communicate with each other and with other physiological systems. We will use an unbiased approach to examine cytokine/chemokine profiles from humans with major depressive disorder and mice exposed to a variable stress model. Using flow cytometry we will determine which peripheral cells are being altered by stress and are releasing the depression signature cytokines. To then examine the functional contribution of these cells and cytokines we will use a combination of bone marrow transplantation and monoclonal antibody therapy to induce or block the effects of stress in our murine model.

 

  • The peripheral immune system sex specifically alters plasticity in the brain.

These studies will test the hypothesis that the peripheral immune system sex specifically alters plasticity in areas of the brain associated with depression and anxiety. In males we have found that bone marrow transplantation from a stress susceptible donor to a host leads to increases in excitatory inputs onto inhibitory cells in the reward circuitry of the brain. Therefore, there is increased inhibition of areas of the brain involved in processing pleasurable experience. This is combined with the finding that these bone marrow transplantations from stressed animal make the host more sensitive to stress susceptibility. Therefore, we believe that these changes in circuitry contribute to anhedonia, a key symptom of depression. Here we will expand this research to understand how cross sex bone marrow transplantation alters plasticity in reward and cognitive circuitry. Preliminary data indicates that males given female bone marrow become stress susceptible whereas females given male bone marrow transplants become stress resilient.  We examine the contribution of the peripheral and central immune system to these phenomena in order to delineate how these peripheral signals are entering the brain and acting on neuronal plasticity.

  • Hodes GE, Menard C, Russo SJ. Integrating Interleukin 6 into depression diagnosis and treatment. Neurobiology of Stress. In Press.
  • Stelzhammer V, Ozcan S, Gottschalk MG, Steeb H, Hodes GE, Guest PC, Rahmoune H, Wong EHF, Russo SJ, Bahn S. Central and peripheral changes underlying susceptibility and resistance to social defeat stress – a proteomic profiling study. Diagnostics in Neuropsychiatry. In press.  
  • Hodes GE, Walker DM, Labonte B, Nestler EJ, Russo SJ. Understanding epigenetic basis of sex differences in depression. Journal of Neuroscience Research. In press.
  • Golden SA,Heshmati, M, Flanigan M,  Christoffel DJ, Guise K, Pfau ML, Aleyasin H, Menard C, Zhang H, Hodes GE, Bregman D, Khibnik L, Tai J, Rebusi N, Krawitz B, Chaudhury D, Walsh JJ, Han MH, Shapiro ML, Russo SJ.  Basal forebrain projections to the lateral habenula modulate aggression reward, Nature, June 29; 534 (7609): 688-92.
  • Menard C, Pfau ML, Hodes GE, Russo SJ. Immune and neuroendocrine mechanisms of stress vulnerability and resilience. Neuropsychopharmacology, 2016 July 6, doi: 10.1038/npp.2016.90. Epub ahead of print.
  • Hodes GE, Pfau ML, Purushothaman I, Ahn HF, Golden SA, Christoffel DJ, Menard C, Aleyasin H, Magida J, Flannigan M, Heshmati M, Koo JW, Feng J, Turecki G, Neve R,  Shen L, Nestler EJ, Russo SJ.  Sex differences in nucleus accumbens transcriptome profiles associated susceptibility versus resilience to sub-chronic variable stress. Journal of Neuroscience, Dec 16; 35 (50): 16362-76.
  • Hodes, GE, Kana V, Menard C, Merad M, Russo SJ. Neuroimmune mechanisms of depression. Nature Neuroscience Oct;18(10):1386-93. doi: 10.1038/nn.4113.
  • Costi S, Hodes GE, Schwartz J, Horn S, Collins KA, Iosifescu DV, Russo SJ, Murrough JW. P.1.f.020 Association between peripheral interleukin 6 and brain response to positive stimuli in a depressive spectrum. European Neuropsychopharmacology. Sept; 25, Supp 2, S235-236.
  • Christoffel DJ, Golden SA, Heshmati M, Walsh JJ, Pfau ML, Hodes GE, Khibnik L, Aleyasin H, Flanigan M, Rebusi N, Russo SJ. Excitatory transmission at thalamo-striatal synapses mediates susceptibility to social stress. Nature Neuroscience, Jul; 18(7); 962-4. doi: 10.1038/nn.4034.
  • Menard C, Hodes GE, Russo SJ. Pathogenesis of depression:  Insights from human and rodent studies. Neuroscience, May 30 . pii: S0306-4522 (15) 00495-9.doi: 10.1016/jneuroscience.2015.05.053 .
  • Nugent BM, Wright CL, Shetty AC, Hodes GE, Lenz KM, Mahurkar A, Russo SJ, Devine SE, McCarthy MM.  Brain feminization requires active repression of masculinization via DNA methylation. Nature Neuroscience, May 18 (5): 690-7 doi: 10.1038nn.3988.
  • Koo JW, Mazei-Robison MS, LaPlant Q, Egervari G, Braunscheidel KM, Adank DN, Ferguson D, Feng J, Sun H, Scobie KN, Damez-Werno DM, Ribeiro E, Pena CJ, Walker D, Bagot RC, Cahill ME, Anderson SA, Labonte B, Hodes GE,
  • Browne H, Chadwick B, Robison AJ, Vialou VF, Dias C, Lorsch Z, Mouzon E, Lobo MK, Dietz DM, Russo SJ, Neve RL, Hurd YL, Nestler EJ. Epigenetic basis of opiate suppression of BDNF gene expression in the ventral tegmental area. Nature Neuroscience, Mar; 18 (3): 415-22.  doi: 10.1038/nn.3932.
  • Hodes GE, Pfau ML, Leboeuf M, Golden SA, Christoffel DJ, Bregman D, Rebusi N, Heshmati M, Aleyasin H, Warren BL, Labonte B, Horn S, Lapidus KA, Steizhammer V, Wong  EHF, Rothermundt M, Bahn S, Krishnan V, Bolanos- Guzman CA, Murrough JW, Merad M,  Russo SJ. Individual differences in the peripheral immune system promote susceptibility versus resilience to social stress. Proceedings of the National Academy of Sciences. Nov 11;111(45):16136-41.
  • Hodes GE, Sex, Stress and Epigenetics: Regulation of Behavior in Animal Models of Depression. Biology of Sex Differences, Jan 21; 4 (1):1.
  • Hodes GE, Russo SJ. Animal Models of Depression and Anxiety. Neurobiology of Mental Illness 4th Edition. Editors: Charney D, Buxbaum J, Sklar P, Nestler EJ. Oxford University Press, ISBN: 9780199934959.
  • Golden SA, Christoffel DJ, Heshmati, M. Hodes GE, Magida J, Davis K, Cahill ME, Dias C, Ribeiro E, Ables JL, Gonzalez-Maeso J, Neve RL, Ghose S, Tamminga CA, and Russo SJ. Epigenetic regulation of synaptic remodeling in depression. Nature Medicine. Mar; 19 (3) 337-44.
  • Holloway T, Moreno J, Umali A, Rayannavar V, Hodes GE, Russo SJ, Gonzalez-Maeso J. Pre-natal stress induces schizophrenia like alterations of 5-HT2A and mGlu2 receptors in the adult offspring: Role of maternal immune system. Journal of Neuroscience, Jan 16; 33 (3): 1088-98.
  • Hodes GE, Russo SJ.The Neurobiology of Depression and Anxiety: How do we change from models of drug efficacy to understanding mood and anxiety disorders?  Drug Discovery and Medicinal Chemistry for Psychiatric Disorders. Editors Rankovic Z, Bingham M, Nestler EJ, Hargreaves R. Royal Society of Chemistry Publishing. London UK ISBN: 978-1-84973-365-6; DOI: 10.1039/9781849734943.06159.
  • Christoffel DJ, Golden SA, Heshmati M, Graham A, Birnbaum S, Neve RL, Hodes GE, Russo SJ.  Effects of Inhibitor of kB Kinase Activity in the Nucleus Accumbens on Emotional Behavior. Neuropsychopharmacology. Nov; 37 (12): 2615-23.
  • Hodes GE, Brookshire B, Hill-Smith TE, Teegarden SL, Berton O, Lucki I. Strain Differences in the effects of chronic corticosterone exposure in the hippocampus Neuroscience, Oct 11; 222: 269-80.
  • Dietz DM, Sun H, Lobo MK, Gao V, Chadwick B, Koo JW, Mazei-Robinson MS, Damez-Werno D, Maze I, Dietz KC, Ferguson D, Christoffel D, Ohnishi Y, Hodes GE, Zheng Y, Neve RL, Russo SJ, Nestler EJ.  Rac1 is essential in cocaine-induced structural plasticity of nucleus accumbens neurons. Nature Neuroscience, Jun; 15 (6): 891-6.
  • Dietz DM, LaPlant Q, Watts EL, Hodes GE, Russo SJ, Feng J, Oosting RS, Vialou V, Nestler EJ.  Paternal transmission of stress-induced pathologies. Biological Psychiatry, 70 (5): 408-14.
  • Cohen JW, Louneva N, Han LY, Hodes GE, Wilson RS, Bennett DA, Lucki I, Arnold SE. (2011) Chronic corticosterone exposure alters postsynaptic protein levels of PSD-95, NR1 and synaptopodin in the mouse brain. Synapse, 65 (8): 763-70.
  • Hodes GE, Hill-Smith TE, Lucki I.  Fluoxetine treatment induces dose dependent alterations in depression associated behavior and neural plasticity in female mice. Neuroscience Letters, 484 (1) 12-6.
  • Hodes GE, Hill-Smith TE, Suckow RF, Cooper TB, Lucki I.  Sex-specific effects of chronic fluoxetine treatment on neuroplasticity and pharmacokinetics in mice. Journal of  Pharmacology and Experimental Theraputics, 332 (1) 266-73.
  • Hodes GE, Yang L, VanKooy J, Santollo J, Shors TJ. Prozac during puberty:  Distinctive effects on neurogenesis as a function of age and sex. Neuroscience, 163 (2) 609-17.
  • Balu DT, Hodes GE, Anderson BT, Lucki I. Enhanced sensitivity of the MRL/MpJ mouse to neuroprotective and behavioral effects of chronic antidepressants. Neuropsychopharmacology, 34 (7), 1764-73.
  • Balu DT, Hodes GE, Hill TE, Ho N, Rahman Z, Ring RH, Rosenweig-Lipson S, Schechter LE, Lucki I. Flow cytometric analysis of BrdU incorporation as a high-throughput method for measuring adult neurogenesis in the mouse. Journal of Pharmacological and Toxicological Methods, 59 (2), 100-7.
  • Dalla C, Whetstone AS, Hodes GE, Shors TJ. Stressful experience has opposite effects on dendritic spines in the hippocampus of cycling versus masculinized females. Neuroscience Letters, 449 (1), 52-6.
  • Hodes GE, Shors TJ.Learning during middle age: A resistance to stress? Neurobiology of Aging, 28 (11), 1783-8.
  • Hodes GE, Shors TJ.Distinctive stress effects on learning during puberty. Hormones and Behavior, 48 (2), 163-171.

Georgia Hodes

Georgia Hodes
  • (540) 232-8684
  • ghodes@vt.edu
  • Hodes Lab/Faculty
    Integrated Life Science Building, Room 2009 (office);
    Room 2103 (lab)
    1981 Kraft Drive
    Blacksburg, VA 24061