Brian M. Davis, PhD

  • Professor, Neurobiology

Phone

412-648-9745

E-mail

bmd1@pitt.edu

Education & Training

PhD, State University of New York at Stony Brook (1983)

Location

E1457 Biomedical Science Tower

Research Interest Summary

Cellular and molecular mechanisms of central and peripheral nervous system development and plasticity

My graduate and postgraduate training focused on spinal cord anatomy and physiology with an emphasis on plasticity. Starting in the 1990’s, my research began to explore how growth factors regulate development and adult function of the sensory nervous system.  This work was followed by studies of afferent and efferent function of sensory neurons that innervate visceral organs (including colon, bladder and pancreas) and skin.  In these studies, I incorporated anatomical, behavioral, optogenetic and electrophysiological techniques to identify underlying mechanisms that cause persistent changes in sensory neurons that contribute to pathophysiological states responsible for chronic pain, neurogenic inflammation and cancer.  My interest in primary sensory neurons has led me to develop three main research programs that are ongoing in my laboratory.

 

The first is research program explores normal function of visceral afferents primarily in the colon, bladder and pancreas and how afferent function changes with inflammation.  Our goal is to understand how acute pain transitions into chronic pain and to identify targets for new therapies that could prevent this transition. 


The second is a project that uses optogenetics to express novel opsins (channelrhodopsin and halorhodopsin) and genetically engineered calcium sensors (GCaMP) in specific populations of colon sensory neurons, enteric neurons of the colon and interstitial cells of Cajal (ICC).  We are also using mice that express novel opsins in colon epithelium to study how these cells communicate with neurons innervating the colon.  The goal of these studies is to develop a comprehensive connectome that describes how stimuli originating in the colon are integrated by colonic epithelium, visceral sensory neurons and the enteric and autonomic nervous systems.  

The third a is translational program that employs a mouse model of human pancreatic ductal adenocarcinoma (PDAC) to study the role of the nervous system in pancreatic cancer, both with respect to pain and neurogenic inflammation, which we hypothesize contributes to cancer progression.  During these studies we found that denervation of the pancreas slowed or halted development of tumors.  Given that 100% of these mice normally develop cancer, this finding was remarkable.  Our most recent studies suggest a non-inflammatory mechanism for this observation; sensory neurons express high levels of immune checkpoint proteins that may produce a pro-tumorigenic environment, allowing the incipient cancer cells to avoid immunosurveillance.  This would explain why denervation prevents cancer progression; loss of neurally-mediated immunosuppression allows the immune system to detect and destroy early cancer cells.  We are currently following up on this work via a collaboration with Dr. Dario Vignali, a leader in cancer immunobiology

Stopczynski R.E., D.P. Normolle, D. J. Hartman, H. Ying, J. J. DeBerry, K. Bielefeldt, A. D. Rhim, R. A. DePinho, K. M. Albers, and B. M. Davis. (2014) Neuroplastic changes occur early in the development of pancreatic ductal adenocarcinoma. Cancer Res. 74: 1718-17-27. PMID: 24448244

 

DeBerry J.J., Saloman J.L., Dragoo B.K., Albers K.M., and Davis B.M. (2015) Artemin immunotherapy is effective in preventing and reversing cystitis-induced bladder hyperalgesia via TRPA1 regulation. J Pain, doi: 10.1016/j.jpain.2015.03.014. [Epub ahead of print] PMID: 25892657

 

Baumbauer, K.M., J.J. DeBerry, P.C, Adelman, R.H. Miller, J. Hachisuka, K.H. Lee, S.E. Ross, H.R. Koerber, B.M. Davis and K.M. Albers (2015). Keratinocytes can modulate and directly initiate nociceptive responses. Elife, 2015. 4:1-14; DOI: 10.7554/eLife.09674.001

 

Saloman, J.L., K.M Albers, D. Li, D.J. Hartman, H.C. Crawford, E.A. Muha, A.D. Rhim, and B.M. Davis (2016). Ablation of sensory neurons in a genetic model of pancreatic ductal adenocarcinoma slows initiation and progression of cancer. PNAS; 113(11): 3078-3083; PMID: 26929329

 

Saloman J.L., Singhi A.D., Hartman D.J., Normolle D.P., Albers K.M. and B.M. Davis (2018) Systemic depletion of nerve growth factors inhibits disease progression in a genetically engineered model of Pancreatic Ductal Adenocarcinoma. Pancreas 2018. 47(7):856-863.

 

DeBerry, J.J., Samineni, V.K., Copits, B.A., Sullivan, C.J., Vogt, S.K., Albers, K.M., Davis, B.M., and Gereau Iv, R.W. (2018). Differential Regulation of Bladder Pain and Voiding Function by Sensory Afferent Populations Revealed by Selective Optogenetic Activation. Front Integr Neurosci 12, 5. PMC5816063

 

Makadia PA, Najjar SA, Saloman JL, Adelman P, Feng B, Margiotta JF, Albers KM, Davis BM. Optogenetic Activation of Colon Epithelium of the Mouse Produces High-Frequency Bursting in Extrinsic Colon Afferents and Engages Visceromotor Responses. J Neurosci. 2018;38(25):5788-98. PMCID: PMC6010562.

 

Smith-Edwards KM, Najjar SA, Edwards BS, Howard MJ, Albers KM, Davis BM. Extrinsic Primary Afferent Neurons Link Visceral Pain to Colon Motility Through a Spinal Reflex in Mice. Gastroenterology. 2019;157(2):522-36 e2. Epub 2019/05/11. doi: 10.1053/j.gastro.2019.04.034. PubMed PMID: 31075226.