Shaun Brothers, Ph.D.
Assistant Professor of Psychiatry
Description of Research
Dr. Brothers’ research focus is on drug discovery. Dr. Brothers is trained as a pharmacologist and expert in drug discovery and development. In his graduate work identified the mode of action of a pharmacological chaperone for the gonadotropin-releasing hormone receptor, a G protein coupled receptor. From this work, Dr. Brothers became ever more interested in novel therapeutics and sought postdoctoral training in an academic drug discovery center. The Scripps Research Institute had started a Florida Campus dedicated to the discovery and development of novel therapeutics. Dr. Brothers joined Scripps Florida in 2006 and initiated several new drug discovery projects including several that utilized the high throughput screening capabilities available at Scripps. After Scripps Florida, Dr. Brothers was recruited to the University of Miami as an Assistant Professor in the Department of Psychiatry and Behavioral Sciences under Dr. Charlie Nemeroff. Dr. Brothers is also a founding member of the Center for Therapeutic Innovation at the Miller School.
Dr. Brothers has embarked on a number of successful compound discovery efforts including several aimed at cancer targets. Dr. Brothers works daily with medicinal chemists, pharmacologists, screeners, engineers, drug metabolism experts, behaviorists and other experts to advance compounds. One such compound is currently being utilized by the research community (SF-11, sold by Tocris). In another notable project, Dr. Brothers has worked to develop novel BRD4 inhibitors. Such compounds could be useful for the treatment of a number of different cancers including glioblastoma multiforme (GBM). These compounds have been licensed out into a spin out company working to develop the compounds for GBM. Dr. Brothers has worked with researchers at the Mayo Clinic and at the University of Illinois Chicago to identify novel methyltransferase G9a inhibitors that may be useful for the treatment of pancreatic cancers. Dr. Brothers’ current work also includes the identification of novel MLL3 inhibitors for use in research relating to cancer via an ultra high throughput screening effort being conducted at the Sanford-Burnham Institute.
Another area of interest is in rare genetic disorders. Dr. Brothers led a team that identified novel compounds that upregulate alpha-iduronidase in patient derived cells, an enzyme that is deficient in mucopolysaccharidosis I (MPSI) patients. MPSI is a rare autosomal recessive disorder in which the affected patient typically dies by the age of 10 years old. The compounds are being advanced with the hope of reaching the clinic within a year. There are a number of intractable diseases related to MPSI and Dr. Brothers is spearheading a program to address more of them.
In addition to his work in drug discovery, Dr. Brothers maintains a research program in neurosciences, particularly in addiction. Dr. Brothers’ work has uncovered novel mechanisms involved in substance dependence and abuse. This work is being pursued with a view that epigenetics controls the neuroplasticity underlying brain adaptation to addictive substances. It is clear that epigenetics plays a role in all biological processes, however, aside from the cancer field, very little has been done to elucidate these roles in physiology and disease. Finally, Dr. Brothers is well known in the fields of drug discovery and therefore sits as a reviewer on both the Drug Discovery in Neuroscience (DDNS) and the Molecular Probes Special Emphasis Panel (MDCN-C) study sections for the NIH.
- Discovered the mechanism of action for pharmacological chaperones.
- Discovered several novel chemotypes for disease-oriented targets by high throughput screening efforts.
- Developed novel inhibitors for bromodomain containing proteins such as BRD2/3/4.
- Identified a novel pathway in PTSD by use of novel compounds developed in the lab.
- Identified a potential novel therapy for mucopolysaccharidosis I.
- Developed the first ever selective nociceptin receptor agonists.
- Identified novel epigenetic pathways in disease.
- Discovered a novel role for G9a in pancreatic cancer.
- Identified and developed MLL3 inhibitors.
Selected Cancer-Related Publications
Collaborating in the Multidisciplinary Research Program(s):