Rensselaer Polytechnic Institute has named medical chemist Christopher L. Cioffi as its Thomas and Constance D’Ambra Professor of Medicinal Organic Chemistry. As a doctoral student in the laboratory of Mark Wentland at Rensselaer Polytechnic Institute, Dr. Cioffi, B.S. ’94 and Ph.D. ’00, witnessed the birth of Samidorphan, a compound that is now part of the FDA-approved schizophrenia treatment Lybalvi. This semester, his career comes full circle as Dr. Cioffi returns to Rensselaer.

As a top-tier technological research university, Rensselaer invests in outstanding researchers, sophisticated research platforms, and strategic partnerships to address the most pressing global challenges of the 21st century. The institute’s commitment to cross-disciplinary research continues to expand through investments in core facilities and hiring world-class faculty.

“Our goal is to design and develop novel drugs that will eventually make their way to the clinic and ultimately to patients who have an unmet medical need. This may include treating diseases for which there are currently no pharmacotherapies available or for diseases where the current standard of care significantly underserves the patient population,” said Dr. Cioffi, of his research group. Much of his research is aimed at disorders of the central nervous system (CNS), with current projects focusing on neuropathic pain and ocular diseases. Emerging projects will focus on various psychiatric and neuro-developmental areas. “We are pursuing an array of different projects intended to both enable a better understanding of CNS indications and improve our chances of delivering a drug that will ultimately reach patients.”

At the molecular level –whether assembling a protein the body needs to survive, or finding and neutralizing an invader— biology is like a three-dimensional jigsaw puzzle, with complementary molecules fitting together at a binding site to trigger the next step along the path of a process. Many medicines treat illness in like fashion, binding to pockets of molecular targets in the body to block or promote a process. A medicinal chemist designs and synthesizes small molecules that fit where needed and only where intended.

“We are thrilled to bring Professor Chris Cioffi to Rensselaer as the D’Ambra Chair,” said Curt Breneman, dean of the Rensselaer School of Science. “His excellent track record for innovative research and proven expertise in medicinal organic chemistry will further elevate both fundamental and applied drug discovery efforts at Rensselaer.”

Dr. Cioffi pairs his expertise in medicinal chemistry with that of other researchers, (i.e., pharmacologists, computational chemists, and structural biologists) who understand the pharmacology and structure of his intended molecular target and who gather information on its binding pocket. In addition to assessing the in vitro affinity and mechanism of binding between his drug and the molecular target, Dr. Cioffi’s collaborators will measure the drug’s potential in vivo efficacy in a preclinical model that recapitulates the human disease state that it is intended to treat.

“By working with several world-class collaborators who are experts in their respective areas, we have had the opportunity to learn about the pharmacology of diverse biological systems,” Dr. Cioffi said. “We employ standard practices applied for early-stage small molecule drug discovery research. Using state-of-the-art organic synthetic, computational, and medicinal chemistry methods, we carefully design and synthesize molecules to engage key binding pockets identified on molecular targets that have been validated to play a pathological role in a specific disease state. We then send our newly synthesized compounds to our collaborators who are working to get a better understanding of the drug binding event and the ensuing pharmacology resulting from modulating the activity of the molecular target. We continue this iterative process until we have identified molecules that give us the binding affinity, physicochemical/pharmacokinetic properties, and toxicological profile we desire in order to develop potent, safe, and efficacious orally bioavailable drugs.”

After earning both his bachelor’s in chemistry and doctorate in organic chemistry at Rensselaer, Dr. Cioffi went on to a 16-year career as a medicinal chemist and drug discovery scientist at Curia (formerly Albany Molecular Research Inc.), the company co-founded by Thomas D’Ambra. His work contributed to 26 patents issued or published during that time. Among his industrial and research successes, he was co-inventor of compounds created to treat dyslipidemia, Stargardt disease, irritable bowel syndrome, and two novel series of selective and potent inhibitors of glycine transporter 1 that exhibited potential for treating symptoms associated with schizophrenia. Many of the compounds he co-invented are in various phases of preclinical development or clinical trials.

He joins Rensselaer from the Albany College of Pharmacy and Health Sciences (ACPHS), where he was an associate professor of medicinal chemistry, and continued his research with several projects treating indications for ophthalmic diseases, such as atrophic age-related macular degeneration and Stargardt disease, and safe, effective, non-opioid treatments for chronic neuropathic pain. His work is currently supported by research grants from the National Institutes of Health. In 2020, he earned the ACPHS Researcher of the Year Award.

And he brings home with him the legacy of his mentor, Professor Emeritus Mark Wentland, in whose laboratory Dr. Cioffi recalls learning many invaluable lessons.

“He is a tremendous mentor and a dear friend to me, very patient, kind, and honest. Mark was extraordinarily supportive of the people working in his lab and of the students in his classroom,” Dr. Cioffi said.