Section 'Sub' Navigation:
Dr. Ana M. Pajor
Ana M. Pajor, Ph.D.
Skaggs School of Pharmacy and Pharmaceutical Sciences
Research Summary: Transporters
The focus of our research is the SLC13 family of plasma membrane transporters for citric acid cycle intermediates, such as citrate and succinate (CAC). CAC intermediates regulate physiological processes ranging from renal function, fatty acid synthesis and energy metabolism. Cellular concentrations of CAC are determined in part by the activity of plasma membrane proteins from the SLC13 family of Na+-coupled di- and tricarboxylate transporters. The SLC13 members are key drug targets for a variety of metabolic disorders including Type 2 diabetes. Inactivation of SLC13 homologs (INDY gene) results in lifespan extension through mechanisms related to caloric restriction, whereas deletion of the Na+/citrate transporter (NaCT, slc13a5-/-) in mice results in increased energy expenditure and resistance to weight gain. Mutations in NaCT are found in epileptic encephalopathy. The long term objective of our studies is to understand the specific roles of the SLC13 transporters in metabolic regulation under normal and disease conditions.
B.Sc. Biology, Ottawa (1978); M.Sc. Biology, Ottawa (1982); Visiting student, Karolinska Institute (1982-83); Ph.D. Physiology, Arizona (1988); Postdoctoral training, UCLA (1988-91).
Awards and Honors:
NIH Research Career Development Award (1996-01); Executive Leadership in Academic Medicine Fellow (2003-04); J. Biol. Chem. Editorial Board (2000-05).
Chair ad interim, Department of Physiology and Molecular Biophysics, University of Texas Medical Branch, Galveston, TX (2003-04).
- Scientific Writing, Director (SPPS/BIOM/PHAR 284)
- Principles of Pharmacology and Physiology, Winter quarter. Co-director. (SPPS 248)
- Renal system. (SPPS 234)
- Pharmacogenomics (SPPS 219/Pharm 235)
Key Contributions to Pharmaceutical Sciences
- Expression cloning of NaDC1.
- Identification of other SLC13 family members, including NaDC3, SdcS, hNaS1.
- Identification of renal SGLT2.
- Identification of NaDC1 inhibitor.
Selected Recent Publications (view more)
- Pajor AM, Sun NN (2013). Nonsteroidal anti- inflammatory drugs and other anthranilic acids inhibit the Na+/dicarboxylate symporter from Staphylococcus aureus. Biochemistry 52:2924-2932
- Schlessinger A et al. (2014). Determinants of substrate and cation transport in the human Na+/dicarboxylate cotransporter NaDC3. J. Biol. Chem. 289:16998-17008
- Colas, C. et al. (2015). Structure-based identification of inhibitors for the SLC13 family of Na+/dicarboxylate cotransporters. Biochemistry 54:4900-4908.
- Klotz, J et al. (2016) Mutations in the Na+/citrate cotransporter NaCT (SLC13A5) in pediatric patients with epilepsy and developmental delay. Mol. Med. (in press)
- Pajor, AM et al (2016) Molecular basis for inhibition of the Na+/citrate transporter NaCT (SLC13A5) by dicarboxylate inhibitors. Mol. Pharmacol. 90:1-11.
Potential Collaborative Programs with the Pharmaceutical Industry
- 25 years experience with sodium-coupled transporters for glucose, nucleosides, dicarboxylates, sulfate
- Target validation/ADME
- Heterologous expression systems for medium throughput screening of transporter function; Experience in adapting MTS to HTS in collaboration with Pharma
- In depth MoA systems for understanding interaction of transporters with inhibitors (e.g. mammalian cell cultures, Xenopus oocyte, two electrode voltage clamp, radiotracer assay, site-directed mutagenesis