Health Sciences Library & Informatics Center
MSC09 5100
1 University of New Mexico
Albuquerque, NM 87131-0001

Find Faculty at UNM Health Sciences Center

Larry A Sklar, PhD

 



Contact Information:
08 4640
Albuquerque NM 87131-0001
505-272-4814
lsklar@salud.unm.edu

Department:
SOM Pathology Department

Interests:
Signal transduction, cell adhesion, Leukocyte Biology, High Throughput technologies for molecular assembly and drug discovery

Flow Cytometry
High-Throughput Drug Discovery

Big questions:

  • How can flow cytometry be used in high-throughput systems for drug discovery?
  • What are the molecular interactions that occur at cell surfaces and lead to intracellular signaling?
Methodology:
  • Flow cytometry
NM Integrated Discovery
  • Target expression and physiology (Prossnitz)
  • Analysis of ligand-receptor and protein-protein interactions; display and assembly on particles; solubilization of TM proteins (Sklar)
  • High throughput flow cytometric screening (Edwards); front-end sample handling (Buranda, Zwartz)
  • Virtual screening and cheminformatics for small molecule drug discovery (Oprea)
  • Probe Chemistry and Synthetic Optimization (Arterburn, ChemDiv)
Cell Adhesion: Real-time Analysis
  • Ligand affinity (fluorescent native ligands and small molecules)
  • Fluorescent LDV small molecule binds to VLA-4 (Chigaev, Larson)
  • Cell avidity under “single bond”conditions
  • Comparison of cellular and molecular rates (Chigaev, Zwartz)
  • Integrin conformation on live cells using FRET.
  • When VLA-4 is activated it elongates (Chigaev, Buranda)
  • Integrated Shear Device (Zwartz)


Publications:
* Young SM, Curry MS, Ransom JT, Ballesteros JA, Prossnitz ER, Sklar LA, Edwards BS. High-throughput microfluidic mixing and multiparametric cell sorting for bioactive compound screening. J Biomol Screen. 9:103-11, 2004

* Zwartz G, Chigaev A, Foutz T, Larson RS, and Sklar, LA. Relationship between molecular and cellular dissociation rates for VLA-4/VCAM-1 interaction in the absence of shear. Biophysical J. 86:143-1252 2004.

* Sklar LA, Tsuji H, Edwards BS, Larson R, Schuyler M. Eosinophil traffic in the circulation following allergen challenge. Allergy, 59:596-605, 2004.

* Simons PC, Biggs SM, Waller A, Foutz T, Cimino DF, Guo Q, Neubig RR, Tang WJ, Prossnitz E, and Sklar LA. Real-Time Analysis of Ternary Complex on Particles: Direct Evidence for partial agonism at the agonists-receptor.G protein assembly step of signal transduction. JBC,279, 13514-21, 2004.

* Chigaev A, Buranda T, Dwyer D. Prossnitz ER. Sklar LA. FRET of Cellular VLA-4 conformation. BPJ, 86:1243-1252, 2004.

* Bartsch JW, Waller A, Mammoli AA, Buranda T, Sklar LA, Tran HD and Edwards BS. An Investigation of Liquid Carry-over and Sample residual for the HyperCyt Sample Delivery System, Analytical Chem 76:3810-17, 2004.

* Simons P, Shi M, Foutz T, Lewis J, Buranda T, Lim WK, Neubig R, Garrison J, Prossnitz ER, Sklar LA, Beads Coated With Epitope Tagged G Proteins Assemble Complexes of Ligand-Receptor-G Protein for Detection by Flow Cytometry. Mol Pharm. 64, 1227-1238, 2003.