Ream Al-Hasani

Ream Al-Hasani is a British neuroscientist and pharmacologist as well as an Assistant Professor of Anesthesiology at Washington University in St. Louis, Missouri. Al-Hasani studies the endogenous opioid system to understand how to target it therapeutically to treat addiction, affective disorders, and chronic pain.

Early Life and Education

Al-Hasani grew up in the United Kingdom. Al-Hasani’s family moved from Iraq to the UK for her father’s academic career before she was born. Her parents planned on returning to Iraq after her birth but decided against it due to war in the Middle East. Al-Hasani was the only Muslim girl in her school, and though there were not many Middle Eastern role models in science, she became fascinated by the effects of drugs on the brain and decided to pursue a career in academia.

Al-Hasani completed her undergraduate degree at the University of Portsmouth in the UK, graduating with a degree in Pharmacology. After completing her undergraduate degree, Al-Hasani pursued an internship in industry at GlaxoSmithKline where she studied neurodegenerative diseases and neuroinflammation. Al-Hasani’s year-long internship studying neuroscience in industry inspired her to pursue a PhD in neuropharmacology. She would become the first woman in her family to obtain a doctorate.

Funded by the Medical Research Council, Al-Hasani was able to pursue her graduate studies at the University of Surrey in England. Al-Hasani was interested in exploring the interactions between adenosine and dopamine receptors in morphine addiction for her PhD, so she sought co-mentorship from Dr. Ian Kitchen, Professor of Neuropharmcology, and Dr. Susanna Hourani, Professor of Pharmacology.

In 2010, Al-Hasani and her colleagues in the Kitchen Lab published a paper in the European Journal of Neuroscience exploring the influence of genetic variability on heroin addiction. When they compared a strain of highly inbred mice to typical control mice, they found differences in the behavioral effects of heroin and differences in the neurobiological substrates mediating these differences. Specifically, they found that highly inbred mice had much higher sensitivity to the rewarding properties of heroin yet inbred did not display increased location upon administration of heroin unlike control mice. When they looked for the neurobiological substrates of these effects, they found that heroin decreased mu opioid receptor (MOP-r) density in controls but not in the inbred mice, MOP-r stimulated binding was two fold higher in controls compared to inbreds, and heroin increased expression of dopamine transporters in inbred mice but not in controls. The differences they observed in MOP-r activations and expression as well as dopamine transporter expression may underlie the variability we see in vulnerability to heroin addiction.

In 2011, Al-Hasani published a first author paper in Neuroscience exploring the interaction between dopamine signalling and adenosine signalling in the ventral tegmental area (VTA). Since adenosine A(2A) receptors have been known to modulate neurotransmitter systems and modulate neural activity in the striatum, she sought to see if this was also true in the VTA. When Al-Hasani knocked out A(2A) receptors and looked the dopamine receptor 2 (D2) mediated inhibition in the VTA, she found that A(2A) knockouts had D2 receptor desensitization leading to reduced maximal inhibition. Her finding provides insight into how drug addiction might change adenosinergic and dopaminergic signalling in the brain’s reward system. A follow up to this finding was published in Neuropharmacology in 2013 looking at the ability of A(2A) receptors to modulate cholinergic signalling through interactions with nicotinic acetylcholine receptors.

Al-Hasani took time to travel after her PhD and then decided to move to America for her postdoctoral work. She joined the lab of Dr. Michael Bruchas in the Department of Anesthesiology at Washington University School of Medicine in St. Louis. Under the mentorship of Dr. Bruchas, Al-Hasani began to explore the kappa opioid system and associated neural circuitry to understand its role in driving motivated behaviors. Al-Hasani wrote a first-athour review paper in 2011 discussing the opioid system in the brain and how opioid receptors not only mediate intracellular signal transduction pathways to modulate molecular and cellular responses as well as their role in behaviors associated with analgesia, reward, depression, and anxiety. In 2013, Al-Hasani published a first author paper in Neuropsychopharmacology where she investigated the interactions between noradrenergic (NA) and dynorphin/kappa opioid systems in the forebrain. She found that kappa opioid receptor(KOR)-induced reinstatement of cocaine CPP was potentiated when beta-adrenergic signalling was blocked and that the interactions between adrenergic signalling and KOR signalling occur external to the locus coeruleus. Her findings were novel since the interaction between the KORs and the NA system had not been previously known, and she established its role in the reinstatement of cocaine drug seeking behavior. Also in 2013, Al-Hasani first authored a second paper exploring the effects of stress on the kappa opioid system in the context of drug relapse. She found that various stressors cause dysregulation of kappa opioid circuitry, but interestingly, mild stressors cause adaptive changes in the kappa opioid circuitry that might be protective against drug relapse.

In addition to her discoveries about the kappa opioid system, Al-Hasani also helped create innovative technologies in the Bruchas Lab such as improved wireless optogenetic technologies that allow for neural circuit modulation without animal movement being constrained by tethering. She also helped to merge this wireless optogenetic tool with pharmacology such that various compounds can be administered to the brain while certain neural circuits are being activated or inhibited to explore the effects of these compounds on neural circuit function and behavioral output. Al-Hasani continued with tool development during her tenure in the Bruchas Lab and in 2018 published a novel method to be able to detect endogenously released peptides from active neural circuits in vivo. She combined in vivo optogenetics with microdialysis so that researchers can stimulate genetically identified neurons and also detect the peptides that are released that might be mediating neural circuit changes and behavioral outputs.

In 2015, Al-Hasani helped elucidate the mechanisms by which the locus coeruleus noradrenergic (LC-NE) system generates stress-induced anxiety in rodents. They found that activation of the LC-NE neurons increases stress-induced anxiety and aversion and that inhibition attenuates these behaviors. They also found that specifically the corticotropin-releasing hormone positive neurons in the LC that receive inputs from the central amygdala are the neural subpopulation within the LC responsible for mediating the anxiety-like behaviors. Later in 2015, Al-Hasani published a first-author paper in Neuron describing distinct functions of two different subregions of the nucleus accumbens (NAc) that are mediated by dynorphin-kappa opioid receptor (KOR) signalling. Specifically, she found that stimulating dynorphinergic cells in the ventral shell of the NAc elicits aversive responses via KOR activation while stimulating dynorphinergic cells in the dorsal shell of the NAc elicits appetitive behaviors mediated by  KOR signalling. Al-Hasani’s work in the Bruchas Lab has helped to elucidate the role of the dynorphin-kappa opioid system in modulating affective states and in mediating drug reinstatement. It also led to her winning an NIH Pathway to Independence Award (K99/R00) which provided her the funding to start her own lab.

Career and Research

In 2017, Al-Hasani was recruited to stay at Washington University School of Medicine, along with her husband Dr. Jordan McCall, and take on a primary appointment as an Assistant Professor in the Department of Pharmaceutical and Administrative Sciences at the St. Louis College of Pharmacy as well as an adjunct appointment as an Assistant Professor in the Department of Anesthesiology at the Washington University School of Medicine (WUSM). Al-Hasani and McCall were the first two researchers to be appointed positions at the new Center for Clinical Pharmacology, formed by a merging of the St. Louis College of Pharmacy and WUSM. Together, Al-Hasani and McCall will help pave the way for the center to achieve its goal of developing and identifying new therapeutic approaches for pain treatment.

Al-Hasani’s lab focuses on understanding the neural circuitry involved in addiction, stress, and chronic pain by specifically focusing on the opioid system to elucidate targets for future therapies. By building and using innovative tools for in vivo neural circuit dissection, Al-Hasani and her team study the role of the kappa opioid system in the generation of negative affective states that might accompany chronic pain, withdrawal, and preclude nicotine cessation. Already, Al-Hasani has helped to better dissect physical pain from its emotional affective counterpart in a study published in Neuron in 2019. Al-Hasani, along with a team of other researchers, sought out to understand how the kappa opioid system mediates the emotional response to pain, which can lead to drug overdose and co-morbid psychiatric conditions such as depression. They targetted their investigation to the ventral shell of the nucleus accumbens (NAc), which Al-Hasani had previously shown to be involved in negative affective states. They found that pain recruits the dynorphin-kappa opioid system in the NAc, and that the dynorphinergic cells are more active during inflammatory pain due to a decrease in inhitbory inputs onto these cells. By blocking dynorphinergic kappa opioid receptor signalling in the shell of the NAc, they are able to alleviate the decrease in motivation that results from the experience of pain.  These findings show that the kappa opioid system is modulating the emotional aspects of the experience of pain and that this may be a better target for therapies in the future that both alleviate the negative affect associated with pain and are not as addictive as current pain treatments. In April, 2020, Al-Hasani was awarded the Young Investigator Grant from the Brain and Behavior Research Foundation. This funding will continue to support her work towards creating less addictive therapies for chronic pain patients, a population of patients which are in dire need of innovative therapies.

Beyond her direct contributions to scientific innovation in the WUSM community, Al-Hasani has helped to mentor the younger generation of scientists and create a space for them to enter the pipeline from a young age. Al-Hasani and McCall recently created a program for undergraduates to explore research opportunities and advance current research at Washington University. They have both hosted undergraduates in their labs and sent them to conferences to present their findings to the broader scientific community.

Awards and Honors

• International Narcotics Research Conference Young Investigator Award
• Young Investigators Grants from the Brain and Behavior Research Foundation
• "Pathway to Independence Award" from NIDA

Select Publications

• Massaly, Nicolas & Copits, Bryan & Wilson-Poe, Adie & Hipolito, Lucia & Markovic, Tamara & Yoon, Hye & Liu, Shiwei & Walicki, Marie & Bhatti, Dionnet & Sirohi, Sunil & Klaas, Amanda & Walker, Brendan & Neve, Rachael & Cahill, Catherine & Shoghi, Kooresh & Gereau, Robert & Mccall, Jordan & Al-Hasani, Ream & Bruchas, Michael & Moron, Jose. (2019). Pain-Induced Negative Affect Is Mediated via Recruitment of The Nucleus Accumbens Kappa Opioid System. Neuron. 102. 10.1016/j.neuron.2019.02.029.
• Al-Hasani R, Wong JT, Mabrouk OS, McCall JG, Schmitz GP, Porter-Stransky KA, Aragona BJ, Kennedy RT, Bruchas MR. detection of optically-evoked opioid peptide release. Elife. 7. PMID 30175957 DOI: 10.7554/eLife.36520
• G. Shin*, A.M. Gomez*, R. Al-Hasani,* (co-first author), Y. Jeong*, J. Kim*, Z. Xie, A. Banks, J. Kurniawan, J. Tureb, Z. Guo, S. Han, C.J. Yoo, J. Lee, S.H. Lee, J. Yoon, S.I. Park, S.Y. Bang, Y. Nam, M.C. Walicki, V.K. Samineni, A.D. Mickle, S.Y. Heo, J.G. McCall, T. Pan, L. Wang, X. Feng, T. Kim, J.K. Kim, Y. Li, Y. Huang, R.W. Gereau IV, J.S. Ha, M.R. Bruchas, and J.A. Rogers (2017). Subdermal near field wireless optoelectronics for broad applications in optogenetics. Neuron (Featured article). Feb 8;93(3):509-521. PMID: 28132830.
• N. Massaly, J.A. Moron, R. Al-Hasani (2016). A trigger for opioid misuse: Chronic pain and stress dysregulate the
• mesolimbic pathway and kappa opioid system. Frontiers in Neuroscience, Nov 7;10:480. PMID: 27872581.
• E.R. Siuda, R. Al-Hasani, J.G. McCall, D.L. Bhatti, M.R. Bruchas (2016). Chemogenetic and optogenetic activation of Gas signalling in the basolateral amygdala induces acute and social anxiety-like states. Neuropsychopharmacology, Jul;41(8): 2011-13. PMID: 26725834.
• P. Namburi, R. Al-Hasani, G.G. Calhoon, M.R. Bruchas, K.M. Tye (2015). Architectural representation of valence in the limbic system. Neuropsychopharmacology, Jun; 41 (7): 1697-715. PMID: 26647973.
• T. Trang, R. Al-Hasani, D. Salvemini, M.W. Salter, H. Gutstein, C.M. Cahill (2015). Pain and poppies: the good, the bad, and the ugly of opioid analgesics. Journal of Neuroscience, Oct 14;35(41):13879-88. PMID 26468188.
• Al-Hasani R, McCall JG, Bruchas MR. Exposure to chronic mild stress prevents kappa opioid-mediated reinstatement of cocaine and nicotine place preference. Frontiers in Pharmacology. 4: 96. PMID 23964239 DOI: 10.3389/fphar.2013.00096
• Al-Hasani R, McCall JG, Foshage AM, Bruchas MR. Locus coeruleus kappa-opioid receptors modulate reinstatement of cocaine place preference through a noradrenergic mechanism. Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 38: 2484-97. PMID 23787819 DOI: 10.1038/npp.2013.151
• Al-Hasani R, Bruchas MR. Molecular mechanisms of opioid receptor-dependent signaling and behavior. Anesthesiology. 115: 1363-81. PMID 22020140 DOI: 10.1097/ALN.0b013e318238bba6
• Al-Hasani R, Foster JD, Metaxas A, Ledent C, Hourani SM, Kitchen I, Chen Y. Increased desensitization of dopamine Dâ‚‚ receptor-mediated response in the ventral tegmental area in the absence of adenosine A(2A) receptors. Neuroscience. 190: 103-11. PMID 21669258 DOI: 10.1016/j.neuroscience.2011.05.068