The Lankenau Institute for Medical Research
Department: LIMR Chemical Genomics Center
Association: Resident Faculty
Other Appointments: Sr. Investigator; Chief Scientific Officer, Small Molecule Therapeutics
Awards and Honors
During his 20-year career in industry, Dr. Reichman has been a director of drug discovery at major biotechnology companies, including GD Searle, Berlex Biosciences, Ligand Pharmaceuticals, Oncogene Sciences and DuPont Pharma. Dr. Reichman founded and directs the LIMR Chemical Genomics Center (LCGC), where he designed and built a patented automated repository and screening technology to help accelerate drug discovery. His current research focuses on developing and applying ultra-high throughput screening technologies to discover new drug synergies for treating diseases that have high unmet medical need, including neurodegeneration and diabetes complications.
He is an editor of several leading drug discovery journals, and serves as President and Chairman of the Board for the International Chemical Biology Society.
Neurodegeneration: ALS Amyotrophic lateral sclerosis (ALS; also known as Lou Gehrig’s disease) is a progressive neurodegenerative disorder that affects motor neurons in the brain and spinal cord. The disease is categorized as a protein misfolding disorder. Understanding how protein misfolding causes diseases like ALS, Alzheimer’s, Parkinson’s and Huntington’s diseases, as well as the loss of brain function with aging, is an important, overarching theme in neuroscience research today.
Dr. Reichman’s research focuses on the novel hypothesis that a dynamic subunit-exchange process between isoforms of superoxide dismutase-1(SOD1) is a potential mechanism to explain ALS genesis and progression in certain forms of the familial disease, and possibly a subset of patients inflicted with the spontaneously occurring disorder.
Dr. Reichman is developing and applying a fundamental new type of multiplexed-drug screening technology (i.e., testing pools of drugs together) to discover synergistic combination drugs to treat ALS by stabilizing SOD1. Drug discovery for small molecules that stabilize protein interactions is an unexplored area in drug screening science. The research is funded by a DOD IDEA award and a drug development award from the ALS Association.
Diabetes Complications Serious complications are a significant risk for Type I/II diabetics. Recently, Alzheimer’s disease has been strongly linked to diabetes, and this has been called Type III diabetes. The mechanistic link between diabetes and the development of life-threatening complications remains one of the great scientific mysteries in disease physiology.
A leading hypothesis is that complications are caused by protein glycation—the binding of glucose or other reducing sugars (e.g. fructose) to proteins — which leads to formation of advanced glycation end products (AGEs). The AGEs are believed to cause vascular inflammation and deterioration in sensitive tissues, including kidney, retina and the brain. The enzyme fructosamine-3-kinase (F3K) reacts with glycated proteins to form the glucose metabolite, 3-deoxyglucosone (3DG). This molecule induces oxidative stress and vaso-inflammatory responses. It is also a precursor to the formation of AGEs.
Recent work indicates that 3DG levels are elevated in diabetics, and higher levels appear to be associated with more extensive nephropathy, retinopathy and neuropathy. Dr. Reichman’s hypothesis is that the most direct way to lower protein glycation and 3DG levels in humans is to inhibit F3K with a drug. His team is developing new F3K assays and performing high throughput screening (HTS) to discover such a drug. This research is funded by Dynamis Pharmaceuticals Inc. (Elkins Park, PA).
Ultra-High Throughput Screening for Synergy (uHTSS): Two decades of intense technology advances in drug screening at pharmaceutical companies has not improved drug-approval success rates. A reason could be that the focus of early-stage drug discovery has been predominantly on single drug targets. Yet complex disorders, including diabetes complications and neurodegeneration, are believed to be driven by multiple mechanisms. Additionally, patent expirations and changes in healthcare regulations require greater innovation in preclinical research and development (R&D). Dr. Reichman is leveraging a patented uHTSS technology as a new path for revealing unexpected medicinal utility in combinations of FDA-approved drugs. He calls this highly innovative concept “synergistic drug repositioning.” The technology could be applied to revive the promise of failed clinical drug candidates (i.e., shown to be safe but having weak efficacy), and to explore the medicinal potential of combinations of certain nutraceuticals and over-the-counter products. Double-Blinded Drug Discovery (DBD2®) Dr. Reichman and his team also have established a new open-innovation model for public-private partnering and resource sharing called
Double-Blinded Drug Discovery: The aim is to accelerate innovation in pharmaceutical R&D by bringing university and industrial scientists together in collaboration to validate the medicinal potential of new target proteins investigated at universities, and to discover new medicines having a faster track to clinical trials.
To achieve this objective, he developed, validated and patented a unique infrastructure to collect, preserve and distribute the vast chemical libraries owned by pharmaceutical companies for joint translational research with universities equipped for HTS. The patented Nanotube Automated Repository Server is capable of high throughput storage and retrieval of over 10 million samples with a robot arm working within a room-sized freezer. Dr. Reichman’s goal is to serve as an agent in catalyzing new ways for university and industry “drug hunters” to explore vast biological and chemical space far more efficiently, looking for synergistic combination drugs to treat complex diseases.
LIMR Chemical Genomics Center (LCGC) was established to have a significant impact on challenging areas of translational R&D. His lab helps to bridge the gap between pharmaceutical companies and universities through Double-Blinded Drug Discovery (DBD2)®, an open-innovation framework that protects intellectual property in public-private partnerships, while allowing research to progress in preclinical R&D. Utilizing several patented technologies, LCGC distributes small-molecule libraries to a broad network of collaborators around the world to validate novel biological targets and for drug discovery, aiming to treat diseases with high patient need. His research emphasis is on developing and applying innovative HTS technologies to more efficiently discover synergistic drug combinations.
A High-Throughput Assay for Rho Guanine Nucleotide Exchange Factors Based on the Transcreener GDP Assay. Reichman M, Schabdach A, Kumar M, Zielinski T, Donover PS, Laury-Kleintop LD, Lowery RG. J Biomol Screen. 2015 Jul 20
Interview with Mel Reichman, PhD. Reichman M, Glaser V. Assay Drug Dev Technol. 2015 Jan-Feb;13(1):11-5.
Identification and characterization of small molecule human papillomavirus E6 inhibitors. Malecka KA, Fera D, Schultz DC, Hodawadekar S, Reichman M, Donover PS, Murphy ME, Marmorstein R. ACS Chem Biol. 2014 Jul 18;9(7):1603-12. doi: 10.1021/cb500229d. Epub 2014 Jun 2. PubMed PMID: 24854633; PubMed Central PMCID: PMC4145632.
Meglumine exerts protective effects against features of metabolic syndrome and type II diabetes. Bravo-Nuevo A, Marcy A, Huang M, Kappler F, Mulgrew J, Laury-Kleintop L, Reichman M, Tobia A, Prendergast GC. PLoS One. 2014 Feb 27;9(2):e90031.
Opening the lead generation toolbox. Simpson PB, Reichman M. Nat Rev Drug Discov. 2014 Jan;13(1):3-4.
Development of a Novel Screening Strategy Designed to Discover a New Class of HIV Drugs. Cheng N, Lee SK, Donover PS, Reichman M, Schiffer CA, Hull-Ryde EA, Swanstrom R, Janzen WP. J Lab Autom. 2013 Dec 4;19(3):297-303.
New informatics and automated infrastructure to accelerate new leads discovery by high throughput screening (HTS). Donover PS, Yohn M, Sim M, Wright A, Gowda S, Allee C, Schabdach AR, Reichman M. Comb Chem High Throughput Screen. 2013 Mar;16(3):180-8.