the sklar laboratory




Biographical Highlights in New Mexico

Dr. Sklar was recruited to New Mexico to direct the National Flow Cytometry Resource at Los Alamos and to develop a biotechnology research program at the University of New Mexico. From 1990-2002 he served as Director or Co-Director of the P41 National Flow Cytometry Resource at Los Alamos (P41RR01315) with responsibilities in research, collaboration, service, training, and dissemination. Beginning in 1998, Sklar led a team of colleagues in the development of high throughput flow cytometry for signal transduction and drug discovery. This work began as an NIH-funded Bioengineering Research Partnership (BRP GM60799/EB00264), which was funded in the inaugural year of that NIH program and brought together cell and molecular biology, biophysics, instrumentation hardware and software and microfluidics. This team was involved in discovery research that involved membrane steroid receptors of the G protein-coupled receptor (GPCR) class and has discovered small molecules that differentiate the classical nuclear estrogen receptors from the novel membrane estrogen receptors. The team has also developed real-time methods to examine affinity, avidity and conformation of integrin receptors involved in cell adhesion (R01 HL08162).

Dr. Sklar has a track record in innovation and high throughput biotechnology, the use of computer modeling in biomedical research and team building. These teams are multidisciplinary, crossing academic boundaries and unifying institutions across our geographic region. The team has continued evolving and innovating, adding synthetic chemistry and cheminformatics, to allow small molecule discovery first as an NIH Roadmap Molecular Libraries Screening Center (1U54MH074425) and now as a Probe Production Center (1U54MH084690). Continuing team innovation and evolution includes translational work, taking small molecules into animal disease models, using isotopes and radioimaging.

The success of this research has been recognized by the W.M. Keck Foundation, which awarded UNM, under Sklar’s leadership, funding to develop a small animal PET/SPECT isotope imaging resource. This imaging capability is having a significant impact on the Cancer Center and our institution, by nucleating infrastructure that unifies efforts in basic and translational science, animal models of disease and relationships with our National Labs through the New Mexico Center for Isotopes in Medicine. Taken together, these activities have contributed in a significant way to the Health Sciences Center’s intellectual property portfolio and led to the incorporation of a new biotechnology startup company, IntelliCyt in Albuquerque. Co-invented by Sklar at UNM, and commercialized by IntelliCyt, the HyperCyt high through flow cytometry platform has been distributed internationally by Beckman Coulter. These activities serve as a model for commercialization efforts that have been identified as critical to the development of biotechnology in our region.

Trained as a physical chemist, but working with industrial partners, physicians, biomedical researchers, and National Lab engineers and physicists, Sklar has a long history translating between medical and non-medical researchers. He has mentored more than 60 trainees including more than 10 faculty members as well as a team of freshman high school girls in a drug discovery project supported by his BRP grant that won the New Mexico State Supercomputing Competition in 2000. He has more than 360 publications and patents in the areas of leukocyte biology, molecular assembly in signal transduction and cell adhesion, and innovative technology for molecular assembly and drug discovery.

Innovation, Discovery and Translation

Starting in the 1990’s and in part as an outgrowth of his experience as director and co-director of the National Flow Cytometry Resource at Los Alamos National Laboratories, Sklar led a team of basic biomedical scientists and biomedical engineers at UNM in the creation of a technological platform for high throughput screening by flow cytometry. Since that time, the team has played a significant role in the biological applications of small molecules to probe cell physiology, in technology development for small molecule discovery, and in translation of discovery into the clinic and the commercial world. Current small molecule targets include, but are not limited to drug efflux transporters (with Tegos, Larson, Winter), signaling and receptor systems (with Edwards, Oprea, Prossnitz, Wu), integrins and leukocyte biology (with Chigaev), and GTPases (with Wandinger-Ness), as well as yeast as model systems, virus-cell interactions (with Buranda and Hjelle), and bacterial pathogenesis (with Tegos). Sklar has led or contributed to competitive funding applications resulting in programmatic discovery funding totaling ~ $50M since 1998.

Integrins

Since the start of his professional faculty career at Scripps in 1980, Sklar has been interested in the cellular pathway through which leukocytes respond to the cellular environment via adhesion and motility. In the current decade, this has led our team to study integrins as nanomachines that integrate force, conformation and signaling. These studies have involved the real-time analysis of integrin physiology, conformation, and affinity (both β1 and β2 integrins), as well as both extracellular and intracellular regulation by small molecules that serve as potential therapeutic agents. We have identified a number of small molecules that regulate integrin function and have developed real-time molecular tools for analysis of integrin function. Our results are addressing the implications of integrin regulation in oncology and inflammation in cells and animal models, and hopefully soon in clinical trials. Funding in excess of $10M in leukocyte biology has been derived through individual grants as well as program grants.

Infrastructure

Sklar has contributed to the development of infrastructure at UNM HSC to support colleagues and shared resources culminating in the award of $9.6M for renovation and capital equipment for the conversion of Tri-Services Building to the Innovation, Discovery and Training Complex. IDTC houses the University of New Mexico Center for Molecular Discovery, Center for Digestive Disease Research, and the Department of Emergency Medicine. Through awards from NIH (R24 CA88399) and the W.M. Keck Foundation and others, Sklar has contributed to the development of Cancer Center Shared Resources, NIEHS Center Biotechnology Core, and CTSC Translational Technology Resource.