Please note: The University of Texas Health Science Center at San Antonio will now be called "UT Health San Antonio."

Search Program Faculty/Research

Karl Rodriguez, Ph.D.

Karlrodriguez cropped (2)

RESEARCH

My long-term research goal is to understand the role of molecular chaperones in protein homeostasis and how proteostasis influences healthspan and longevity. Molecular chaperones, namely heat shock proteins (HSPs), play a key role in maintaining protein quality, preventing protein unfolding and aggregation and influencing the rates of protein degradation via either the proteasome or autophagy. During aging, most organisms have a greater load of damaged or misfolded proteins to target for degradation. This condition is exacerbated by a decline in the efficacy of proteolytic machinery and leads to an accrual of the aggregation-prone cytotoxic proteins that underlie several age-associated pathologies (e.g., Alzheimer’s disease, Parkinson’s disease, sarcopenia). We study these pathologies in the lab.

My lab recently discovered that heat shock protein 25kDa (HSP25) correlated with maximum lifespan potential in rodent muscle and liver tissue. The mechanisms and regulatory processes by which HSP25 is responds to stress within a cell and this regulation influences both cellular and organ health and lifespan is unknown and presents a gap of knowledge in the field of chaperone biology. One of the main projects in the lab is to discover this mechanism in the context of aging and neurodegenerative disease using the Caenorhabditis elegans worm model system. So far we have discovered that HSP25 overexpression positively affects lifespan and mitigates the toxicity of both polyglutamine and tau aggregates.

We have expanded upon this project to look at other small heat shock chaperones and their role in health and longevity in the worm. These roles have led us to look at nutritional stress and inflammatory changes with age and disease. The lab does not only use worms as a model system. Mechanistic discoveries in worms are used to inform future projects in cell culture systems (immortalized and primary), and in animal models such as mice and the long-lived naked mole-rat (Heterocephalus glaber). In the vertebrate systems we examine physiology and behavior in our animals as well as cell and molecular biology.

Selected Publications

Rodriguez KA, Valentine JM, Kramer DA, Gelfond JA, Kristan DM, Nevo E, Buffenstein, R. Determinants of rodent longevity in the chaperone-protein degradation network. Cell Stress Chaperones. 2016 May; 21(3):453-66. doi 10.1007/s12192-016-0672-x. PMID: 26894765.

Rodriguez KA, Li K, Nevo E, Buffenstein R. Mechanisms regulating proteostasis are involved in sympatric speciation of the blind mole rat, Spalax galili. Autophagy. 2016 April 2; 12(4) 703-04. doi: 10.1080/15548627. PMID: 27050459

Triplett JC, Tramutola A, Swomley A, Kirk J, Grimes K, Lewis K, Orr M, Rodriguez K, Cai J, Klein JB, Perluigi M, Buffenstein R, Butterfield DA. Age-related changes in the proteostasis network in the brain of the naked mole-rat: Implications promoting healthy longevity. Biochim Biophys Acta. 2015 Oct; 1852(10 Pt A):2213-24. doi: 10.1016/j.bbadis.2015.08.002. PMID: 26248058.

Li K, Hong W, Jiao H, Wang GD, Rodriguez KA, Buffenstein R, Zhao Y, Nevo E, Zhao H. Sympatric speciation revealed by genome-wide divergence in the blind mole rat Spalax. Proc Natl Acad Sci U S A. 2015 Sep 22; 112(38):11905-10. doi: 10.1073/pnas.1514896112. PMID: 26340990.

Rodriguez KA, Osmulski PA, Pierce A, Weintraub ST, Gaczynska M, Buffenstein R. A cytosolic protein factor from the naked mole-rat activates proteasomes of other species and protects these from inhibition. Biochim Biophys Acta. 2014 Nov; 1842(11):2060-72. doi: 10.1016/j.bbadis.2014.07.005. PMID: 25018089.

Rodriguez KA, Dodds SG, Strong R, Galvan V, Sharp ZD, Buffenstein R. Divergent tissue and sex effects of rapamycin on the proteasome-chaperone network of old mice. Front Mol Neurosci. 2014 Nov 4; 7:83. doi: 10.3389/fnmol.2014.00083. eCollection 2014. PMID: 25414638.

Assistant Professor of Cell Systems and Anatomy

Education

Ph.D. Molecular Medicine, The University of Texas Health Science Center at San Antonio, 2002

Contact

Email: rodriguezk@uthscsa.edu

Phone: (210) 567-7221

Office: STCBM 3.100.04 

Graduate Students

Courtney Carroll, Ph.D., Post-doctoral Fellow (SABER-IRACDA program)

Chelbee Farnen, Graduate Student (IBMS, CGM discipline)

Aliyah Encarnacion, Research Assistant