Melascend®

About the Founder

From my earliest memories of grammar school, I have always known that my career would center around the life sciences, and my passion to understand the pharmacological and toxicological actions of drugs and xenobiotics.  In 1974, I enrolled at Rutgers University, College of Pharmacy, where I received a Bachelor’s of Science degree in Pharmacy in 1979, and became a Registered Pharmacist in New Jersey in 1980.
Very soon after graduating from Rutgers University, it was clear to me that I needed graduate training to achieve my career goals in pharmaceutical research, and I enrolled in the Joint Graduate Program in Toxicology at Rutgers University and the University of Medicine and Dentistry of New Jersey in 1980.  My research identified mechanisms of interaction and metabolism of a series of aliphatic nitrile compounds with the hepatic cytochrome P-450 monooxygenases.  For this work, I received a Masters of Science degree in 1984.

After a brief period of employment as an industrial pharmacist in Mobil Oil Environmental Health Sciences labs, I enrolled in the graduate program in pharmacology and toxicology at the Philadelphia College of Pharmacy and Science (now University of the Sciences in Philadelphia), working in the laboratory of Dr. Howard Colby.  My research sought to identify and characterize the mechanism by which a well-known diuretic (spironolactone) inhibited androgen production.  This work led to our current understanding of spironolactone as a specific mechanism-based inhibitor of the adrenal steroid 17α-hydroxylase/lyase, that explains some of the endocrine side-effects observed in males, and supported additional uses for the drugs for endocrine disorders in women.  I received a Doctor of Philosophy in Pharmacology and Toxicology in January of 1992.
Also in January of 1992, I accepted a postdoctoral fellowship at SmithKline Beecham Pharmaceuticals, to evaluate the pathogenesis of biliary epithelial cell hyperplasia that was observed in preclinical rodent studies following treatment with several drugs in development.  The project was a joint effort between the departments of investigative toxicology, DMPK, and pathology.  One of the hallmarks of the lesion was its association with cholestasis, which directed me to a variety of animal models of intrahepatic and extrahepatic cholestasis that resulted in a similar lesion of the biliary epithelium.  Through a variety of experiments, it became clear that the growth stimulus was not due to an increased pressure in the lumen of the biliary system, but was rather due to perturbations in the chemical composition of the bile itself.  As the project progressed, it was observed that the rat was particularly sensitive to the development of this lesion, which did not develop in other laboratory species.  Consequently, the company successfully argued with FDA that the lesion was rodent-specific, and not likely to pose a human safety concern.  Therefore, the project ended in 1994 without reaching a firm conclusion about the mechanism of action for biliary hyperplasia.

In June of 1994, I accepted the position of Director of Analytical Services and Test Material Control at International Research and Development Corporation (IRDC), a contract toxicology testing laboratory located in Mattawan, Michigan.  At this time, I also assumed responsibility of Study Director for a variety of general toxicology studies that were performed under GLP guidelines.  In 1995, I became a Diplomate of the American Board of Toxicology (DABT). Also during 1995, IRDCencountered legal difficulties, and the company was sold and renamed MPI Research, and in the process my position was eliminated in June of 1996.
Also in June of 1996, I accepted the position of Associate Scientific Leader at Roche Vitamins Inc., in Parsippany New Jersey, where I was responsible for managing preclinical activities for their animal health drugs.  While at Roche, I had performed a number of studies with Frenolicin-B, an antimicrobial compound.  One of the most disturbing toxicologic findings was the onset of esophageal hyperplasia in rats following oral administration of the compound.  To understand this lesion, a literature search revealed that a rat model of esophageal hyperplasia indeed was produced by feeding a zinc-deficient diet over a period of several weeks.  Curiously, other lines of research revealed that the compound Frenolicin-B was a chelator of divalent cations, and zinc in particular.  I hypothesized that the compound may have caused the lesion indirectly via interference with zinc bioavailability, rather than a more troubling direct mitogenic effect.  I designed a research program to investigate the lesion, and prior to its completion, Roche terminated all activities in their Vitamins division, that was later sold to another company.

After a brief period as a toxicology consultant, I joined Medarex Inc. in October of 2000 as their Director of Project Management, where I was responsible for the preclinical development of their fully-human monoclonal antibodies.  For the next 4 years, I gained a thorough understanding of immunology and the mechanism of action for a variety of therapeutic antibodies.  However, my interest in zinc nutriture during this time only magnified, as I attempted to develop a business case to develop human antibodies for the potential treatment and prophylaxis of a variety of inflammatory and autoimmune diseases that are due, in part, to dysregulation of zinc homeostasis.
With little success, I chose to leave Medarex in 2004 to establish NutrienTech LLC, a nutraceutical development company in St. Louis, Missouri, where I forged a relationship with Dr. Michael Welch, a prominent researcher at Washington University, where he was the Director of Radiological Sciences.  Dr. Welch had developed a chemical synthesis for a form of zinc (63Zn), that emits positrons with a decay half-life of 23 minutes.  Using 63Zn, Dr. Welch and I sought to establish a new positron emission tomography (PET) scanning technique capable of visualizing differences in zinc pharmacokinetics that was associated with specific diseases.  Importantly, this PET scanning created the potential to monitor changes in zinc pharmacokinetics as a biomarker for disease progression and therapeutic response.  Currently, a grant to provide funding for these studies is under review at NIH.

At the same time, my interest with zinc has led to a keen interest in the mechanisms of innate immunity, and in particular, the dynamics of an endogenous protein that recently has been identified as a ligand for the TLR-4 receptor.  The compound, calprotectin (CP), is a heterodimeric protein of the S-100 class, and is the most abundant cytosolic protein in neutrophils and macrophages, where it comprises up to 60% of the total protein repertoire.  The name for CP derives from “calcium”, because the protein has been shown to bind calcium, and “protect” because it has been shown to kill a variety of bacteria and microbial species.  Subsequent research has shown that the antimicrobial action of CP is due to its ability to sequester zinc in the local environment, thereby starving the pathogens of this essential nutrient.  For the past 5 years, research has emerged to support a pivotal role for CP in cell signaling, due to the initiation of cytokine cascades that are associated with dysregulation of zinc homeostasis.  Importantly, these events appear to occur locally in specific tissues where CP is released by a variety of chemical and physical stimuli.  Importantly, the kinetics of CP release under these circumstances do not manifest systemically, and thus, current techniques to isolate and identify CP as a pathogenetic factor have failed to produce any firm conclusions about causality.

Most recently, while investigating potential endogenous metallochaperones that facilitate the kinetics of zinc and other trace minerals (the so-called nutrikines), I became highly interested in melatonin as one of the most important members of this class of compounds.  Interestingly, throughout my career, I had many opportunities to engage in a dialogue with my brother Steve Kossor, a clinical psychologist. On one occasion in 2009, Steve indicated to me that many of his clients that had been diagnosed with an Autism Spectrum Disorder (ASD) also suffered from gastrointestinal disorders that also seemed to be associated with insomnia.  Intrigued by these observations, I hypothesized that perhaps a melatonin deficiency may underlie the onset and progression of ASDs.  Since 2009, I have amassed a library of over 1000 publications that have provided several lines of indirect evidence to suggest that a melatonin deficiency indeed is an important etiological factor for the onset of ASD.

During 2009-2010, I decided to refocus my attention on gainful employment, and In 2011, I joined Eastman Chemical Company as an Associate Toxicologist, a position that I currently maintain.
In 2013, I added Project Management Professional (PMP) to my list of credentials, and I abandoned NutrienTech LLC, and decided to pursue melatonin as a therapeutic for the management of ASD. Also in 2013, I created Syncratic Therapies LLC, a company dedicated to the development of Melascend®, a medical food intended for the specific management of ASD.