LARRY A. SKLAR, Ph.D., Professor, Department of Pathology

Education and Honors:

1970, B.S., Chemistry, University of Chicago; 1976, Ph.D., Chemistry, Stanford University.  1976, Helen Hay Whitney Postdoctoral Fellowship; 1982, Established Investigator, American Heart Association; 1993, Distinguished Performance Award, Los Alamos National Laboratory; 1996, Mentor for Presidential Young Investigator, International Society of Analytical Cytometry; 1999, PI for UNM Bioengineering Consortium; 2000, Mentor for Sandia Prep Champion Team, New Mexico Supercomputing Competition; 2000, UNM Regent’s Professorship.

Research Interests:

Dynamics of Macromolecular Assembly. The UNM Cytometry Group is working on the development of new approaches for the real-time analysis of macromolecular assembly and their application in drug discovery. The applications include GPCR, integrins, and selectins. We have pioneered fluorescence technology to examine assembly mechanisms in living systems, at natural abundance. We have demonstrated the applicability of flow cytometric approaches to the kinetics of assembly of molecular complexes on beads. We have developed a stopped-flow subsecond flow cytometer to analyze time-dependent interactions of ligand with cells and particles and to analyze complex reaction mechanisms. We have developed high throughput screening capabilities in flow cytometry for drug discovery.

Adhesive interactions and vascular biology.  We are investigating the molecular basis of neutrophil and eosinophil adhesion.  We have shown that neutrophil aggregation in suspension involves four adhesive receptors that interact pairwise. We identified PSGL-1 as an L-selectin counter-structure on leukocytes that is responsible for homotypic aggregation.  We are attempting to understand how the selectin and integrin mediated steps are coordinated in cell adhesion.  We integrated a cone and plate viscometer with a flow cytometer to characterize the dependence of adhesion on shear and receptor density.  We have shown that preferential capture of eosinophils by P-selectin may contribute to the accumulation of eosinophils in the lung during asthma. We have recently developed a new fluorescent probe for analyzing the affinity of the b1-integrin, VLA-4, in real-time.

Selected Publications:

Nolan JP and Sklar LA. The emergence of flow cytometry for the sensitive, real-time analysis of molecular assembly. Nature Biotechnology, 16, 833-838, 98. 

Nolan JP, Lauer S., Prossnitz, ER and Sklar LA. Flow Cytometry: A versatile tool for all phases of Drug Discovery. Drug Discovery Today, 4, 173-180. 1998. 

Buranda, T., Lopez, G.P., Keij, J., Harris, R. and Sklar, L.A. Peptides, antibodies, and  FRET on beads in flow cytometry: a model system using fluoresceinated and biotinylated b-endorphin. Cytometry, 37, 21, 1999. 

Edwards, B.E., Kuckuck, F., and Sklar, L.A. Plug-flow flow cytometry:an auomtated coupling device for rapid sequential flow cytometric sample analysis. Cytometry, 37, 156, 1999.  

Bennett, T, Edwards, B.E. Sklar, L.A. and Rogelj, S. Sulfhydryl regulation of L-selectin shedding in neutrophils. Phenylarsine Oxide promotes activation independent L-selectin shedding from neutrophils. J. Immunol. 164:4120-4129, 2000. 

Sklar, L.A., Vilven, J., Lynam, E., Neldon, D., Bennett, T., and Prossnitz, E.R. Solubilization and Display of 7TMR on beads for real-time fluorescence and flow cytometric analysis. In Press, Biotechniques 28, 976-985, 2000. 

Edwards, BS, Curry, MS, Tsuji, H, Brown, D., Larson, RS, and Sklar LA. Expression of P-selectin at Low Site Density Promotes Selective Attachment of Eosinophils over Neutrophils. J. Immunol. 165, 404-410, 2000. 

Ransom, JT, Edwards, BS, Kuckuck, FW, Okun, A, Mattox, ER, and Sklar, L.A.. Flow Cytometry Systems for Drug Discovery and Development. SPIE Proceedings, 3921, 90-100, 2000.