The National Institute on Drug Abuse (NIDA) recently highlighted two papers featuring Susruta Majumdar, PhD, and his colleagues. The Chemistry and Pharmacology Branch of the Division of Neuroscience and Behavior highlighted these articles.
In a study published in Nature Communications in March 2023, researchers from the Center for Clinical Pharmacology unveil promising research in the development of more effective, less addictive, and safer pain management drugs.
In this study “Molecular mechanism of biased signaling at the kappa opioid receptor,” researchers closely examined the κ-opioid receptor (KOR), a molecule in the body that can be targeted by drugs to help manage pain and itch without causing addiction.
Congratulations to Sarah Bernhard for receiving the 2023 Predoctoral Fellowship in Drug Discovery.
Groundbreaking research conducted by Susruta Majumdar, Ph.D., associate professor of medicinal chemistry and pharmacology at University of Health Sciences and Pharmacy in St. Louis, and his colleagues, has identified a method for modifying the chemical properties of the opioid pain reliever, fentanyl, and altering how it binds to opioid receptors on nerve cells.
Through studies conducted in cell lines expressing the opioid receptor and in mice, the modified version of fentanyl was found to be an effective pain reliever with fewer significant side effects. The research, which was recently published in the journal Nature, offers potential avenues for the creation of safer opioid medications.
The paper highlights the work of Susruta Majumdar, Ph.D., associate professor of medicinal chemistry and pharmacology at University of Health Sciences and Pharmacy in St. Louis, and his colleagues who examined the molecular differences between LFT and MP, and how they bind to MU opioid receptors.
Bahaa Elgendy, Ph.D., associate professor of medicinal chemistry at University of Health Sciences and Pharmacy in St. Louis and Lamees Hegazy, Ph.D., associate professor of computational and medicinal chemistry at UHSP, were the recent recipients of a $3.1 million grant from the National Institutes of Health’s National Institute of Neurological Disorders and Stroke to support research focused on the treatment of inflammatory pain.
The five-year grant will allow Elgendy and Hegazy, and their research collaborators, to further investigate the role of the REV-ERB nuclear receptors as a viable target for the treatment of inflammatory pain. Elgendy and Hegazy will leverage the known physiological functions of REV-ERB in chronic inflammation and use a chemical biology approach to identify novel REV-ERV ligands with superior pharmacological profiles, with the goal of advancing the potential therapy to clinical trials.
In 2017, Ream Al-Hasani, Ph.D., assistant professor of pharmaceutical science at University of Health Sciences and Pharmacy in St. Louis, and assistant professor of anesthesiology at Washington University School of Medicine in St. Louis, was recruited as one of the first researchers at the Center for Clinical Pharmacology. Since then, Al-Hasani and her center collaborators from the Department of Anesthesiology at the School of Medicine have been conducting groundbreaking research on the neurological effects of addiction and the brain’s response to pain or stress.
With much of her research focused on the kappa opioid receptor system and its potential to serve as a promising target for the non-addictive management of neuropsychiatric conditions, including pain, Al-Hasani has been engaged in a number of innovative projects, including her work to create new methods for measuring opioid peptides in living systems. Her efforts have resulted in the development of a reliable and reproducible process to allow other research labs to implement and benefit from this technique.
Amynah Pradhan, Ph.D., an award-winning neuroscientist, has been appointed director of the Center for Clinical Pharmacology, effective Sept. 1, 2022. Pradhan joins the center from the Department of Psychiatry at the University of Illinois at Chicago, where she was faculty since 2013 and associate professor with tenure since 2019. At UIC, Pradhan also served as Director of the Graduate Program in Neuroscience since 2019.
As center director, Pradhan will lead the strategic planning efforts for all research growth and development, provide mentorship for trainees and faculty, foster a diverse and inclusive environment to stimulate new and exciting research endeavors, and continue to grow inter-institutional partnerships and collaborations as well as national recognition for the center.
Lamees Hegazy, Ph.D., assistant professor of medicinal chemistry at University of Health Sciences and Pharmacy in St. Louis, was the recent recipient of a three-year, $581,000 grant from the National Institutes of Health’s (NIH) National Institute of Diabetes and Digestive and Kidney Diseases.
Ream Al-Hasani, Ph.D., assistant professor of pharmaceutical science at University of Health Sciences and Pharmacy in St. Louis, was the recent recipient of a five-year, $2.1 million grant from the National Institutes of Health (NIH) to further her research on cold pain hypersensitivity.
Al-Hasani and her research team at the Center for Clinical Pharmacology have been studying the issue of cold hypersensitivity for several years. Utilizing their newly acquired NIH grant, the team will further examine the role of the kappa opioid system in cold hypersensitivity and cold pain.
Bahaa Elgendy, Ph.D., assistant professor of medicinal chemistry at University of Health Sciences and Pharmacy in St. Louis, was the lead author of a recent article featured in the Journal of Medicinal Chemistry’s Perspective series. The series provides a forum for recognized research experts to review and provide their input on active areas of research.
Cyrielle Billon, Ph.D., assistant professor of pharmacology at University of Health Sciences and Pharmacy in St. Louis, has been chosen to serve on the National Institutes of Health (NIH) Center for Scientific Review’s Cell Signaling and Molecular Endocrinology (CSME) study section.
Two articles featuring breakthrough kratom-related research conducted by Soumen Chakraborty, Ph.D., postdoctoral research associate in the Center for Clinical Pharmacology, were published in the Journal of Medicinal Chemistry this fall.
In a recent study published in Nature Biomedical Engineering on November 25, 2021, Jordan McCall, PhD, MPH, alongside Jae-Woong Jeong, PhD, at Korea Advanced Institute of Science and Technology (KAIST), and Sangtae Ha, PhD, at the University of Colorado, Boulder, have developed a method to remotely control brain circuits in multiple animals simultaneously and independently.
By creating a wireless network utilizing implantable devices and equipment integrated with Internet of Things (IoT) technology, scientists have enabled leading-edge, large-scale neuroscience experiments that can study the brains of animals from almost anywhere outside of the lab. The low-cost setup of this system means it can be easily adopted by other labs due to its minimalistic hardware, ease of use, and customizability. Scientists will be able to implement this technology in their existing laboratories with minimal budget concerns to achieve remote access and automate experiments where having a human present could affect the outcomes of the study.
Susruta Majumdar, Ph.D., associate professor of medicinal chemistry and pharmacology at University of Health Sciences and Pharmacy in St. Louis, has been awarded $2 million in grants to further his work to target opioid and non-opioid receptors with the goal of creating safer analgesics for pain relief.
Sineadh Conway, Ph.D., postdoctoral research associate at the Center for Clinical Pharmacology in the Al-Hasani Lab, was a recipient of the Ruth L. Kirschstein Postdoctoral Individual National Research Service Award from the National Institutes of Health (NIH).
Breakthrough research from Ream Al-Hasani, Ph.D., assistant professor of pharmaceutical science at University of Health Sciences and Pharmacy in St. Louis, and her research team at the Center for Clinical Pharmacology, has identified a new pathway in the brain that may contribute to more effective treatments for drug addiction and depression.
Soumen Chakraborty, postdoctoral research associate in the Majumdar labs in the Center for Clinical Pharmacology, was the lead author of a paper recently published in ACS Chemical Neuroscience, which highlighted his research team’s efforts to isolate new, less prevalent alkaloids from the plant kratom.
Sarah has recently joined the labs of Drs. Tao Che and Susruta Majumdar.
In April 2020, Dr. Pieper, president and professor of University of Health Sciences and Pharmacy in St. Louis, announced he would retire in June 2021, following 11 years as president of the University and a 41-year career in academic pharmacy.
Dr. Burris, Alumni Chair in Pharmaceutical Education and vice president for research at University of Health Sciences and Pharmacy in St. Louis, was ranked among the top 150 pharmacologists in the world in the recently released 2020 Highly Cited Researchers List published by Clarivate.
Manish Kumar Madasu, Ph.D., postdoctoral research associate at the Center for Clinical Pharmacology, was the recent recipient of the Toni Shippenberg Young Investigator Award during the KappaCon 2021 Kappa Therapeutics Conference.
The paper highlights a newly discovered molecule with the potential to provide analgesic pain relief with fewer side effects and less addictive properties than opioids. Majumdar and Che’s research team has been studying the molecule to determine its orientation and how it binds to opioid receptors.
On Tuesday, February 23, 2021, the University of Health Sciences and Pharmacy in St. Louis Board of Trustees marked an important moment in the University’s history with the announcement of its fifth president. David D. Allen, R.Ph., Ph.D., FASHP, FNAP, FAPhA, will serve as the University’s next president, with his tenure beginning on July 1, 2021.
Allen will succeed John A. Pieper, Pharm.D., FCCP, FAPhA, FFIP, who has served as the University’s president since August 1, 2010. Pieper announced his retirement in April 2020 and will continue to serve as president until June 30, 2021.
Drs. Susruta Majumdar and Abdelfattah Faouzi recently co-published a paper in the Journal of Medicinal Chemistry highlighting their work to uncover a compound that could play a key role in the future development of alternative therapeutics for pain management.
TLX is an orphan nuclear receptor that plays important roles in neurogenesis, vision, and cancer. Griffett et al. found that both natural and synthetic retinoids bind directly to TLX and regulate its transcriptional activity. Retinaldehyde, an important visual pigment, is the preferential natural retinoid ligand for TLX.
Dr. Alex Evers, Washington University School of Medicine’s Henry S. Mallinckrodt Professor of Anesthesiology and Professor of Developmental Biology [Pharmacology] and Internal Medicine, has accepted the role of interim director of the CCP effective November 9, 2020. During his tenure as Head of the Anesthesiology Department at Washington University, he was a founder of CCP and contributed much to its many ongoing successes. As such he is fully committed to the Center’s continued vibrancy and growth.
University of Health Sciences and Pharmacy in St. Louis has moved a 500 megahertz (MHz) nuclear magnetic resonance (NMR) spectrometer from Washington University School of Medicine in St. Louis to the Academic and Research Building (ARB).
Non-alcoholic fatty liver disease (NAFLD) affects a significant number of people worldwide and currently there are no pharmacological treatments. NAFLD often presents with obesity, insulin resistance, and in some cases cardiovascular diseases. There is a clear need for treatment options to alleviate this disease since it often progresses to much more the much more severe non-alcoholic steatohepatitis (NASH). The REV-ERB nuclear receptor is a transcriptional repressor that regulates physiological processes involved in the development of NAFLD including lipogenesis and inflammation. We hypothesized that pharmacologically activating REV-ERB would suppress the progression of fatty liver in a mouse model of NASH. Using REV-ERB agonist SR9009 in a mouse NASH model, we demonstrate the beneficial effects of REV-ERB activation that led to an overall improvement of hepatic health by suppressing hepatic fibrosis and inflammatory response.
Dr. Majumdar recently received a $100,000 grant from the National Institutes of Health (NIH) to develop compounds to treat neuropathic pain.
The goal for Dr. McCall’s R01 grant is to better understand how chronic stress modifies the ability of central norepinephrine system, an important source of endogenous analgesia, to increase or decrease control of pain. Psychological stress can either suppress or enhance pain, but it is not well understood how this switch occurs. Most evidence suggests that the type and duration of stress differentially modulates the pain experience with acute stress typically thought to be analgesic, while chronic stress is thought to exacerbate pain. In particular, McCall will use mouse models to identify stress-induced adaptations in neural circuits that supply the dorsal spinal cord with norepinephrine.
Elgendy will investigate the estrogen-related receptor alpha (ERRα) and the critical role it plays in regulating genes involved in oxidative stress and inflammation.
Dr. Susruta Majumdar, recently co-authored a paper demonstrating that certain alkaloids from the plant kratom could potentially be developed into a treatment for alcohol use disorder.
Center faculty, Dr. Susruta Majumdar, Dr. Ream Al-Hasani, and Dr. Jordan McCall, were highlighted in NIDA’s “Review of 2019 Achievements in Opioid Research.”
The Center for Clinical Pharmacology was one of four organizations selected as BMO Harris Bank Spirit of St. Louis Award finalists for 2020.
Tom Burris, Ph.D., FAAAS, FAHA, recently received grant funds totaling more than $740,000 from Mallinckrodt Pharmaceuticals.
The International Narcotics Research Conference (INRC), the annual meeting for researchers and clinicians working in the opioid field, will honor Dr. Al-Hasani with the 2020 Young Investigator Award at their upcoming symposium.
P1 student Yearam “Esther” Tak presented her research on cerebral palsy at the American Neurological Association Annual Meeting and the 48th Child Neurology Society Annual Meeting in October.
Brian Kobilka, M.D., professor of molecular and cellular physiology at Stanford University and winner of the 2012 Nobel Prize in chemistry, recently visited St. Louis College of Pharmacy to present his current research. He was invited by the Center for Clinical Pharmacology as part of its 2019-2020 speaker series.
Nociceptin and its receptor are widely distributed throughout the brain in regions associated with reward behavior, yet how and when they act is unknown. Here, we dissected the role of a nociceptin peptide circuit in reward seeking. We generated a prepronociceptin (Pnoc)-Cre mouse line that revealed a unique subpopulation of paranigral ventral tegmental area (pnVTA) neurons enriched in prepronociceptin. Fiber photometry recordings during progressive ratio operant behavior revealed pnVTAPnoc neurons become most active when mice stop seeking natural rewards. Selective pnVTAPnoc neuron ablation, inhibition, and conditional VTA nociceptin receptor (NOPR) deletion increased operant responding, revealing that the pnVTAPnoc nucleus and VTA NOPR signaling are necessary for regulating reward motivation. Additionally, optogenetic and chemogenetic activation of this pnVTAPnoc nucleus caused avoidance and decreased motivation for rewards. These findings provide insight into neuromodulatory circuits that regulate motivated behaviors through identification of a previously unknown neuropeptide-containing pnVTA nucleus that limits motivation for rewards.
“This funding makes what is easily the riskiest project in the lab a much more secure venture. One of the biggest challenges we face using rodents as models of complicated human conditions is that we cannot ask the animals how they feel. A simple question, but a very difficult one to answer. With this award, we will be working to overcome this barrier by extracting detailed information from videos of the animal’s behavior to determine whether they are in pain, or distress. We will use new types of data analysis from mathematics to essentially ask the mice that simple question, “How do you feel?” By the end of this award, we aim to have made strides in identifying stress and pain in animals without having to disturb their daily routine. This approach will hopefully enable new strategies for understanding neural circuit function and therapeutic development.” – Dr. Jordan McCall, PhD, MPH
““What we found through our studies in mice was that the 7-OH metabolite was responsible for inducing most of the pain relief the mice experienced,” said Majumdar. “Through our research, we discovered that the opioid pharmacology of mitragynine is complicated by the role of 7-OH in mediating its activity. In mouse and human liver preparations, the analgesic effects of mitragynine are actually dependent on 7-OH as a metabolic mechanism.” – Dr. Susruta Majumdar, PhD
“I like to call it the forgotten phase of addiction. I look at the negative effects of relapse and examine what physiological and behavioral changes are happening to drive relapse. I’m also looking at whether less severe withdrawal can prevent relapse. My hope is that if scientists thoroughly understand the neurological effects of withdrawal, they can develop better treatments to help those who are addicted to opioids fully recover from their disease.” – Dr. Ream Al-Hasani, Ph.D.
Center faculty and research students attended the symposium to present their recent findings in the lab. Their posters and podium presentations highlighted the research projects carried out during the 2018-2019 academic year.
Welcome Makenzie, McKenna & Marwa!