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Brenner Laboratory for Translational Neuroscience

The Brenner laboratory currently focuses on the development of novel gene- and cell-based therapies for schwannomas caused by neurofibromatosis type 2 related schwannomatosis (NF2-SWN) and related neoplasms. This includes generation of immunotherapies for these tumors.
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Email: gjbrenner@mgh.harvard.edu
gjbrenner@mgh.harvard.edu
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Overview

The Brenner laboratory is a translational research facility focused on developing novel treatments for understanding neurofibromatosis associated tumors.

A primary area of the work involves creating gene- and cell-based immunotherapies for peripheral nervous system tumors, such as those seen in neurofibromatosis, particularly, schwannoma tumors associated with neurofibromatosis type 2 related schwannomatosis (NF2-SWN). The lab was the first to demonstrate efficacy of bacterial therapy for a benign tumor; mechanisms of action include generation of anti-tumor immunity. Using adenovirus-associated vectors, the lab has utilized delivery of ASC and gasdermin transgenes to induce apoptosis in tumor cells. In addition to tumor research, the lab utilizes optogenetics and functional imaging to map brain circuits involved in nociceptive processing and sensitization following nerve injuries. Dr. Brenner's research also extends to studying the mechanism of action of opioids in the brain, aiming to bridge the gap between basic neuroscience and clinical pain management.

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Read More About Our Research
https://www.ncbi.nlm.nih.gov/myncbi/gary.brenner.1/bibliography/public/
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Collaborators

John J Mekalanos, PhD
Professor of Microbiology, Harvard Medical School

The Mekalanos laboratory is engaged in the analysis of bacterial virulence and functional genomics. The goal of these studies is to understand how pathogenic bacteria grow, evade the host immune system and ultimately cause disease. A variety of organisms are currently studied in the laboratory including several Vibrio species and Pseudomonas aeruginosa. Our research encompasses many topics, including: 1) how bacteria sense their environment and modulate the expression of virulence genes, 2) the mechanism of horizontal gene transfer in the evolution of pathogenic strains, 3) how genomic information can be used to identify virulence factors, antigens, and gene products that are essential for cell growth, 4) ecological factors that control emergence and endemic properties of bacterial pathogens, 5) the biochemical function of bacterial virulence factors including protein secretion organelles that display dynamic activity which can be imaged in real time. We use genetic, genomic, proteomic, biochemical, structural, imaging and chemical biological approaches to explore these topics. Where possible, the knowledge gained in our studies is applied to the development of more effective vaccines and small molecule therapeutics.

Publications

Featured Publications
  1. Moynihan JA, Koota D, Brenner G, Cohen N and Ader R. Repeated intraperitoneal injections of saline attenuate the antibody response to a subsequent intraperitoneal injection of antigen. Brain, Behavior, and Immunity. 1989;3:90-96.
  2. Moynihan JA, Brenner G, Koota D, Breneman S, Cohen N and Ader R. The effects of handling on immune function, spleen cell number, and lymphocyte subpopulations. Life Sci. 1990;46:1937-44.
  3. Moynihan JA, Brenner GJ, Ader R and Cohen N. The effects of handling adult mice on immunologically-relevant processes. Ann NY Acad Sci. 1990;650:252-67.
  4. Brenner GJ, Cohen N. Ader R. and Moynihan JA. Increased pulmonary metastases and natural killer cell activity in mice following handling. Life Sci. 1990;47:1813-19.
  5. Brenner GJ, Felten SY, Felten DL, Cohen N and Moynihan JA. Sympathetic nervous system modulation of tumor metastases and host defense mechanisms. J Neuroimmunol. 1992;37:191-202.
  6. Madden KS, Moynihan JA, Brenner GJ, Felten SY, Felten DL and Livnat S. Sympathetic nervous system modulation of the immune system. III. Alterations in T and B cell proliferation and differentiation in vitro following chemical sympathectomy. J Neuroimmunol. 1994;49:77-87.
  7. Brenner GJ, Cohen N and Moynihan JA. Similar immune response to nonlethal infection with Herpes Simplex virus-1 in sensitive (BALB/c) and resistant (C57Bl/6) mice. Cell Immunol. 1994;157:510-24.
  8. Brenner GJ and Moynihan JA. Stressor-induced alterations in immune response and viral clearance following infection with Herpes Simplex virus-type 1 in BALB/c and C57Bl/6 mice. Brain, Behavior, and Immunity. 1997;11:9-23.
  9. Moynihan JA, Kruszewska B, Brenner GJ and Cohen N. Neural, endocrine and immune system interactions: Relevance for health and disease. Advances in experimental medicine and biology. 1998;438:541-49.
  10. Ji RR, Baba H, Brenner GJ and Woolf CJ. Nociceptive specific activation of ERK in spinal neurons contributes to pain hypersensitivity. Nature Neurosci. 1999;2:1114-9.
  11. Ji RR, Befort K, Brenner GJ, Billet S and Woolf CW. ERK activation in the spinal cord mediates gene expression and persistent inflammatory pain. J Neurosci. 2002;2:478-85.
  12. Brenner GJ, Ji RR, Shaffer S and Woolf CJ. Peripheral noxious stimulation induces phosphorylation of the NMDA receptor NR1 subunit at the PCK-dependent site, serine-896, in spinal cord dorsal horn neurons. European J Neurosci. 2004;20:375-84.
  13. Kawasaki Y, Kohno T, Zhuang ZY, Brenner GJ, Wang H, Van Der Meer C, Befort K, Woolf CJ, and Ji RR. Iontropic and metabotropic receptors, PKA, PKC and Src contribute to C-fiber-induced ERK activation and cAMP response element-binding protein phosphorylation in dorsal horn neurons, leading to central sensitization. J of Neurosci. 2004;24:8310-21.
  14. Xia Y, Sidis Y, Mukherjee A, Samad T, Brenner G, Woolf C, Lin HY, and Schneyer A. Localization and action of Dragon (RGMb), a novel BMP co-receptor, throughout the reproductive axis. Endocrinology. 2005;146:3614-21.
  15. Wang H, Kohno T, Amaya F, Brenner GJ, Ito N, Allchorne A, Ji RR, and Woolf CJ. Bradykinin produces pain hypersensitivity by potentiating spinal cord glutamatergic synaptic transmission. J Neurosci. 2005;25(35):7986-92.
  16. Wang H, Ehnert C, Brenner GJ, Woolf CJ. Minireview: Bradykinin and peripheral sensitization. Biol Chem. 2006;387:11-14. PMID: 16497159.
  17. Agarwal N, Pacher P, Tegeder I, Amaya F, Constantin C, Brenner GJ, Rubino T, Michalski CW, Marsicano G, Monory K, Mackie K, Marian C, Batkai C, Parolaro D, Fischer MJ, Reeh P, Kunos G, Kress M, Lutz B,Woolf CJ and Kuner R. Cannabinoids mediate analgesia largely via peripheral type 1 cannabinoid receptors in nociceptors. Nature Neurosci. 2007;10(7):870-9.
  18. Griffin RS, Costigan M, Brenner GJ, Ma CHM, Scholz J, Moss A, Allchorne AJ, Stahl GL, Woolf CJ. Induction of complement in microglia in the spinal cord results in C5a anaphylatoxin release and pain hypersensitivity. J Neurosci. 2007;27(32):8699-8708.
  19. Binshtok A, Wang H, Zimmermann K, Amaya F, Vardeh D, Shi L, Brenner GJ, Ji RR, Bean B, Woolf CJ, and Samad TA. Nociceptors are interleukin-1β sensors. J Neurosci. 2008;28(52):14062-73.
  20. Costigan M, Moss A, Latremoliere A, Johnston C, Verma-Gandhu M, Herbert TA, Barrett L, Brenner GJ, Vardeh D, Woolf CJ, Fitzgerald M. T-Cell infiltration and signaling in the adult dorsal spinal cord is a major contributor to neuropathic pain-like-hypersensitivity. J Neurosci. 2009;18(46):14415-22.
  21. Prabhakar S, Brenner GJ, Tannous BA, Sena-Esteves M and Breakefield XO. Imaging and therapy of experimental schwannomas using HSV amplicon vector encoding apoptotic protein under control of a Schwann cell promoter. Cancer Gene Therapy. 2010;17(4):266-74.
  22. Xia Y, Babitt JL, Bouley R, Zhang Y, Da Silva N, Chen S, Zhuang Z, Samad TA, Brenner GJ, Anderson JL, Hong CC, Schneyer AL, Brown D, Lin HY. Dragon enhances BMP signaling and increases transepithelial resistance in kidney epithelial cells. Journal Am Soc of Nephrology. 2010;21(4):666-77.
  23. Camino D, Murphy S, Heiry M, Barrett LB, Earley TJ, Cook CA, Petrus MJ, Zhao M, D'Amours M, Deering N, Brenner GJ, Costigan M, Hayward NJ, Chong JA, Fanger CM, Woolf CJ, Patapoutian A and Moran MM. TRPA1 contributes to cold hypersensitivity. J Neurosci. 2010;30(45):15165-74. PMID: 21068322.
  24. Saydam O, Ozdener GB, Senol O, Mizrak A, Prabhakar P, Stemmer-Rachamimov AO, Breakefield XO and Brenner GJ. A novel imaging-compatible sciatic nerve schwannoma model. J Neurosci Methods. 2011;195(1):75-77. PMID: 21111000.
  25. Saydam O, Senol O, Wurdinger T, Mizrak A, Ozdeber GB, Stemmer-Rachamimov AO, Yi M, Stephens RM, Krichevsky AM, Brenner GJ, Breakefield XO. Low microRNA-7 in schwannomas stimulates growth through upregulation of three oncogenic signaling pathways. Cancer Research. 2011;71(3):852-61. PMID: 21156648.
  26. Ma CH, Omura T, Cobos EJ, Latremoliere A, Ghasemlou N, Brenner GJ, van Veen E, Barrett L, Sawada T, Gao F, Coppola G, Gertler F, Costigan M, Geschwind D and Woolf CJ. Accelerating axonal growth promotes motor recovery after peripheral nerve injury in mice. J Clin Invest. 2011;121(11):4332-47. PMID: 21965333.
  27. Brenner GJ*, Ma CH*, Omura T*, Samad OA, Costigan M, Inquimbert P, Niederkofler V, Salie R, Sun CC, Lin HY, Arber S, Coppola G, Woolf CJ, Samad TA. The BMP coreceptor RGMb promotes while the endogenous BMP antagonist Noggin reduces Neurite outgrowth and peripheral nerve regeneration by modulating BMP signaling. J Neurosci. 2011;31(50):18391-400 (*these authors contributed equally). PMID: 22171041.
  28. Brenner GJ, Newmark JL and Raemer D. A curriculum and cases for pain medicine crisis resource management education. Anesth and Analg. 2013;116:107-10. PMID: 23223099.
  29. Mizrak A, Bolukbasi MF, Ozdener GB, Brenner GJ, Madlener S, Erkan EP, Ströbel T, Breakefield XO and Saydam O. Genetically engineered microvesicles carrying suicide mRNA/protein inhibit schwannoma tumor growth. Molecular Therapy. 2013;21(1):101-8. PMID: 22910294.
  30. Prabhakar S, Taherian M, Gianni D, Conlon TJ, Fulci J, Brockmann J, Stemmer-Rachamimov A, Sena-Esteves M, Breakefield XO and Brenner GJ. Regression of Schwannomas induced by AAV-mediated delivery of Caspase-1. Hum Gene Ther. 2013;24(2):152-62. PMID: 23140466.
  31. Giblin K, Newmark JL, Brenner GJ, and Wainger BJ. Headache plus: Trigeminal and autonomic features in a case of cervicogenic headache responsive to third occipital nerve radiofrequency ablation. Pain Med. 2014;15(3):473-8. PMID: 24401103.
  32. Przkora R, Antony A, McNeil A, Brenner GJ, Mesrobian J, Rosenquist R, Abouleish A. Do Pain Medicine Fellowship Programs Provide Education in Practice Management? A Survey of Pain Medicine Fellowship Programs. Pain Physician. 2018;21(1):E43-E48. PMID: 29357339.
  33. Ahmed SG, Abdelnabi A, Doha M and Brenner GJ. Schwannoma gene therapy by adeno associated virus delivery of the pore forming protein Gasdermin-D. Cancer Gene Therapy. 2019;26(9-10):259-267. PMID: 30622323.
  34. Ahmed SG, Abdelnabi A, Maguire CA, Doha M, Sagers J, Lewis RM, Muzikansky A, Giovannini M, Stemmer-Rachamimov A, Stankovic KM, Fulci G and Brenner GJ. Gene therapy with apoptosis-associated speck-like protein (ASC), a newly described schwannoma tumor suppressor, inhibits schwannoma growth in vivo. Neuro-Oncology. 2019;21(7), 854–866. PMID: 30977509.
  35. Ahmed SG, Hadaegh F and Brenner GJ. Developing myelin specific promoters for schwannoma gene therapy. Journal of Neuroscience Methods. 2019 May 22;323:77-81. PMID: 31125589.
  36. Taylor NE, Hu L, Pei J, Kukutla P, Abdelnabi A, Hadaegh F, Taylor E, Solt K, and Brenner GJ. The Rostromedial Tegmental Nucleus: a key modulator of pain and opioid analgesia. PAIN. 2019;160(11):2524-2534. PMID: 22160519.
  37. Sagersa JE, Sahina MI, Moona I, Ahmed SG, Stemmer-Rachamimov A, Brenner GJ, Stankovic KM. NLRP3 Inflammasome Activation in Human Vestibular Schwannoma: Implications for Tumor-Induced Hearing Loss. Hearing Research. 2019; Sep 15;381. PMID: 31430634.
  38. Kohan L, Durbhakula S, Zaidi M, Phillips CR, Rowan CC, Brenner GJ, Cohen SP. Changes in Pain Medicine Training Programs Associated with COVID-19: Survey Results. Anesthesia and Analgesia, 2021; 132(3):605-615. PMID: 33177326.
  39. Vlasov K, Pei J, Nehs CJ, Guidera JA, Zhang ER, Kenny JD, Houle TT, Brenner GJ, Taylor NE, Solt K. Activation of GABAergic neurons in the rostromedial tegmental nucleus and other brainstem regions promotes sedation and facilitates sevoflurane anesthesia in mice. Activation of GABAergic Neurons in the Rostromedial Tegmental Nucleus Promotes Sedation and Facilitates Sevoflurane Anesthesia in Mice. Anesthesia and Analgesia, 2021; 132(4):e50-e55. PMID: 33560660.
  40. Kukutla P, Ahmed SG, DuBreuil DM, Ahmed A, Cetinbas M, Fulci G, Aldikacti B, Stemmer-Rachamimov A, Plotkin SR, Wainger B, Sadreyev RI, and Brenner GJ. Transcriptomic signature of painful human neurofibromatosis type 2 schwannomas. Annals of Clinical and Translational Neurology. 2021; 8(7):1508-1514. PMID: 34053190.
  41. Purvis T, Newmark, Brenner GJ, Brodnik D, Kohan L. Pain Education Innovations during a Global Pandemic. Pain Medicine. 2021; 22(9):1891-1896. PMID: 34411245.
  42. Ahmed SC, Maguire CA, Cao SA and Brenner GJ. Delivery of Apoptosis-Associated Speck-Like Protein Containing CARD (ASC): Preclinical Efficacy and Safety. International Journal of Molecular Sciences. 2022; 23(2), 819-834. PMID: 35055004.
  43. Ahmed SC, Oliva G, Shao M, Wang X, Mekalanos JJ and Brenner GJ. Intratumoral injection of schwannoma with attenuated Salmonella typhimurium induces anti-tumor immunity and controls tumor growth. Proc Natl Acad Sci U S A. 2022 Jun 14;119(24):e2202719119. PMID: 35675425.
  44. Ezaka M, Marutani E, Miyazaki Y, Kanemaru E, Selig MK, Ostrom KF, Boerboom SL, Stemmer-Rachamimov A, Bloch DB, Brenner GJ, Ohshima E, Ichinose F. Oral administration of glutathione trisulfide increases reactive sulfur levels in dorsal root ganglion and ameliorates paclitaxel-induced peripheral neuropathy in mice. Antioxidants. 2022 Oct 27;11(11):2122. PMID: 36358494.
  45. Ahmed SC and Brenner GJ. Effect of Antibiotic Treatment on Attenuated Salmonella typhimurium VNP20009 Mediated Schwannoma Growth Control. Anticancer Research. 2023 Jan;43(1):1-6. PMID: 36585175.
  46. Bommakanti K, Seist R, Kukutla P, Cetinbas M, Batts S, Sadreyev RI, Stemmer-Rachamimov A, Brenner GJ and Stankovic KM. Comparative transcriptomic analysis of archival human vestibular schwannoma tissue from patients with or without tinnitus. Journal of Clinical Medicine. 2023; 12(7), 2642. PMID: 31430634.
  47. Ahmed SC, Oliva G, Shao M, Wang X, Mekalanos JJ and Brenner GJ. Culture of attenuated Salmonella Typhimurium VNP20009 in animal-product-free media does not alter schwannoma growth control. Human Vaccines and Immunotherapeutics. 2023 Oct; 19(2). PMID: 37786375.
  48. Boparai N, Kohan L, Brenner G, Purvis T, Brodnik, D, and Newmark J. A Survey of Pain Fellowship Program Directors on Medical Simulation. Pain Medicine. 2025; 26, 938-940. PMID: 40378240.
  49. Brenner GJ, Kueppenbender K, Mao J and Spike J. Ethical challenges and interventional pain medicine. Current Pain and Headache Reports. 2012;16(1):1-8. PMID: 22160519.
  50. Rejaei D, Brenner GJ. Blinded Efficacy Testing of High Frequency Spinal Cord Stimulation. J Anesthesiology and Pain Research. 2018;1(1):1-2.
  51. Parker R, Hirsch JA, Choy E, Schwab J, Brenner GJ and Daye, D. Percutaneous vertebroplasty and unilateral pediculoplasty for treatment of L5 radiculopathy: a case report. Pain Medicine Case Reports. 2021;5-183-187.
  52. McCormick JF, Schatman ME and Brenner GJ. Advanced age as a consideration in spinal cord stimulation. Journal of Pain Research. 2025;18:5911-5918.
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How to reach us

Contact us with inquiries about ongoing studies, collaboration opportunities, or lab resources:
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email
Email: gjbrenner@mgh.harvard.edu
gjbrenner@mgh.harvard.edu
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Call: 617-726-9223
6177269223
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