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Asaf Keller, PhD

Donald E. Wilson, MD, MACP Distinguished Professor

Academic Title:

Professor

Primary Appointment:

Neurobiology

Administrative Title:

Chair of the Department of Neurobiology

Location:

HSF-I, 280G

Phone (Primary):

(410) 706-7307

Education and Training

  • Ben Gurion University, Israel, B. Med. Sci., Medical Sciences, 1985
  • Ben Gurion University, Israel, Ph.D., Neurobiology, 1988
  • The Rockefeller University, New York, Postdoc, Neurophysiology, 1988-1991

Biosketch

I have been studying sensory processing for nearly 40 years, starting with my predoctoral work in neuroanatomy with Edward L. White, continuing with my postdoctoral training in neurophysiology with Hiroshi Asanuma at The Rockefeller, and in my own laboratory. For the past two decades my work has been focused on brain circuits involved in affective disorders, chronic pain and addiction.

On of our projects focuses on the role of the parabrachial complex and its complement of neurons that express CGRP (calcitonin gene-related peptide), and their effects on downstream targets, including the BNST (bed nucleus of the stria terminalis) and the central amygdala. Our work centers also on descending pain modulatory pathways, and on reward pathways—involving thalamus, prefrontal cortex, parabrachial nucleus, periaqueductal gray and related structures—in the affective components of pain, and in drug addiction.

A second project focuses on the mechanisms by which perinatal exposure to teratogens—including opioids, nicotine, cannabis, valproic acid, and insecticides—cause lasting effects on brain circuit and the behaviors they mediate. 

Work in our laboratory takes advantage of multidisciplinary approaches, including in vitro and in vivo electrophysiology, optogenetics, calcium and voltage-sensitive dye imaging, photometry, extracellular recordings of units, field potential and EEG from awake and anesthetized preparations, neuroanatomical tract tracing and immunocytochemical techniques, and related analytical approaches. I also have a demonstrated record of productive collaboration with mathematicians, physicists, and computational neuroscientists to study neuronal networks.

I have been involved in education of undergraduate, graduate and medical students for more than 30 years, and of postdoctoral fellows for nearly as long. I have trained 15 postdoctoral fellows; all but two are in academic science or with government agencies, and 4 are tenured Professors and have NIH funding. I have also trained 22 graduate students. I enjoyed training 13 undergraduate students. I was the associate director, and then director, of an NINDS-funded institutional postdoctoral training grant between 2004 and 2012. Between 1999 and 2002 I directed the Graduate Program in Neuroscience at the University of Maryland, Baltimore. I view my role as an educator of young scientists to be as important and fulfilling as my role as a scientist. Indeed, the two roles are inseparable to me. I strive to create a research environment that will foster the dreams of my trainees, and that will provide them with the conceptual and practical tools necessary to achieve these dreams.

Some of our ongoing and recently completed projects include:

R01NS104297 (mPI: Keller & Masri) NIH/NINDS. Serotonin and Pain Modulation. 6/2019 – 2/2025. Goals: Study the mechanisms by which the serotonergic pathways drive and modulate chronic pain. 

R01DA054905 (mPI: Keller, Lobo, Ament) NIH/NIDA. Lasting Neurological Effects of Perinatal Opioids . 9/2022 – 7/2027. Goals: Study the lasting consequences on brain circuits and genes of perinatal fentanyl exposure.

R01NS099245 (mPI: Keller & Masri)NIH/NINDS. Parabrachial Role in Chronic Pain. 8/15/2017 - 5/32/2023 Goals: Study the mechanisms by which the parabrachial complex in involved in the pathogenesis of chronic pain.

Research/Clinical Keywords

sensory perception, chronic pain, descending pain modulation, drug abuse, substance use in pregnancy

Highlighted Publications

Smith, JA, Ji, Y, Lorsung, R, Breault, MS, Koenig, J, Cramer, N, Masri, R, Keller, A (2023) Parabrachial Nucleus Activity in Nociception and Pain in Awake Mice. J Neurosci, 43:5656-5667. PMC10401640

Keller, A (2023) Pain and its modulation. Oxford Encyclopedia of Sensory Systems, (Ed. Sherman, M) Oxford University Press, New York & Oxford.

Cramer, N, Ji, Y, Kane, MA, Pilli, NR, Castro, A, Posa, L, Van Patten, G, Masri, R, Keller, A (2023) Elevated serotonin in mouse spinal dorsal horn is pronociceptive. eNeuro, 10:ENEURO.0293-23.2023. PMC10698626

Alipio, JB, Riggs, LM, Plank, M, Keller, A (2022) Environmental Enrichment Mitigates the Long-Lasting Sequelae of Perinatal Fentanyl Exposure in Mice. J Neurosci, 42:3557-3569.

Raver, C, Uddin, O, Ji, Y, Li, Y, Cramer, N, Jenne, C, Morales, M, Masri, R, Keller, A (2020) An Amygdalo-Parabrachial Pathway Regulates Pain Perception and Chronic Pain. J Neurosci, 40:3424-3442. PMC7178908

Additional Publication Citations

Torruella-Suárez, ML, Neugebauer, B, Flores-Felix, K, Keller, A, Carrasquillo, Y, Cramer, N (2024) Divergent changes in PBN excitability in a mouse model of neuropathic pain. eNeuro, ENEURO.0416-23.2024.

Olusakin, J, Kumar, G, Basu, M, Calarco, CA, Fox, ME, Alipio, JB, Haga, C, Turner, MD, Keller, A, Ament, SA, Lobo, MK (2023) Transcriptomic profiling of reward and sensory brain areas in perinatal fentanyl exposed juvenile mice. Neuropsychopharmacology, 48:1724-1734. PMC10579237

Ji, Y, Onwukwe, C, Smith, J, Laub, H, Posa, L, Keller, A, Masri, R, Cramer, N (2023) Noradrenergic input from nucleus of the solitary tract regulates parabrachial activity in mice. eNeuro, 10:ENEURO.0412-22.2023. PMC10162360

Nguyen, E, Smith, KM, Cramer, N, Holland, RA, Bleimeister, IH, Flores-Felix, K, Silberberg, H, Keller, A, Le Pichon, CE, Ross, SE (2022) Medullary kappa-opioid receptor neurons inhibit pain and itch through a descending circuit. Brain, 145:2586-2601. PMC9612802. 

Eley, JG, Haga, CB, Keller, A, Lazenby, EM, Raver, C, Rusek, A, Dilmanian, FA, Krishnan, S, Waddell, J (2021) Heavy Ion Minibeam Therapy: Side Effects in Normal Brain. Cancers, 13:6207.

Uddin, O, Arakawa, K, Raver, C, Garagusi, B, Keller, A (2021) Patterns of cognitive decline and somatosensory processing in a mouse model of amyloid accumulation. Neurobiol Pain, 10:100076. PMC8599510

Tsymbalyuk, O, Gerzanich, V, Mumtaz, A, Andhavarapu, S, Ivanova, S, Makar, TK, Sansur, CA, Keller, A, Nakamura, Y, Bryan, J, Simard, JM (2021) SUR1, newly expressed in astrocytes, mediates neuropathic pain in a mouse model of peripheral nerve injury. Mol Pain, 17:17448069211006603. PMC8020112

Alipio, JB, Haga, C, Fox, ME, Arakawa, K, Balaji, R, Cramer, N, Lobo, MK, Keller, A (2021) Perinatal Fentanyl Exposure Leads to Long-Lasting Impairments in Somatosensory Circuit Function and Behavior. J Neurosci, 41:3400-3417. PMC8051687

Uddin, O, Anderson, M, Smith, J, Masri, R, Keller, A (2021) Parabrachial complex processes dura inputs through a direct trigeminal ganglion-to-parabrachial connection. Neurobiology of Pain, 9:100060.

Uddin, O, Jenne, C, Fox, ME, Arakawa, K, Keller, A, Cramer, N (2021) Divergent profiles of fentanyl withdrawal and associated pain in mice and rats. Pharmacol Biochem Behav, 200:173077.

Cramer, N, Silva-Cardoso, G, Masri, R, Keller, A (2021) Control of synaptic transmission and neuronal excitability in the parabrachial nucleus. Neurobiology of Pain, 9:100057.

Alipio, JB, Brockett, AT, Fox, ME, Tennyson, SS, deBettencourt, CA, El-Metwally, D, Francis, NA, Kanold, PO, Lobo, MK, Roesch, MR, Keller, A (2020) Enduring consequences of perinatal fentanyl exposure in mice. Addict Biol, e12895. 

Ji, Y, Rizk, A, Voulalas, P, Aljohani, H, Akerman, S, Dussor, G, Keller, A, Masri, R (2019) Sex differences in the expression of calcitonin gene-related peptide receptor components in the spinal trigeminal nucleus. Neurobiol Pain, 6:100031. PMC6565752

Akintola, T, Tricou, C, Raver, C, Castro, A, Colloca, L, Keller, A (2019) In search of a rodent model of placebo analgesia in chronic orofacial neuropathic pain. Neurobiology of Pain, 6:100033. PMID

Dr. Keller's Listing on PubMed
https://pubmed.ncbi.nlm.nih.gov/?term=asaf+keller

Lab Techniques and Equipment

Work in Dr. Keller's laboratory takes advantage of multidisciplinary approaches, including:

  • in vitro and in vivo electrophysiology
  • optogenetics, calcium and voltage-sensitive dye imaging
  • extracellular recordings of units
  • field potential and EEG from awake and anesthetized preparations
  • neuroanatomical tract tracing and immunocytochemical techniques
  • related analytical approaches

Dr. Keller has a demonstrated record of productive collaboration with mathematicians, physicists, and computational neuroscientists to study neuronal networks.

Links of Interest

Research Projects

Some of our ongoing and recently completed projects include:

R01NS104297 (mPI: Keller & Masri) NIH/NINDS
Serotonin and Pain Modulation
6/2019 – 2/2025
Goals: Study the mechanisms by which the serotonergic pathways drive and modulate chronic pain. 

R01DA054905  (mPI: Keller, Lobo, Ament) NIH/NIDA
Lasting Neurological Effects of Perinatal Opioids
9/2022 – 7/2027
Goals: Study the lasting consequences on brain circuits and genes of perinatal fentanyl exposure.

R01NS099245 (mPI: Keller & Masri) NIH/NINDS
Parabrachial Role in Chronic Pain
8/15/2017 - 5/32/2023
Goals: Study the mechanisms by which the parabrachial complex in involved in the pathogenesis of chronic pain.