Ortiz, Rudy M. K02: Independent Scientist Award Abstract Candidate. Dr. Rudy M. Ortiz is an assistant professor of physiology and nutrition at the University of California, Merced, which is the 10th and newest campus of the University of California system and is the first major research institution of the 21st century. I joined UCM as a member of its founding faculty in 2005, was its first Hispanic faculty member, and recently (02/09) became the first assistant professor at UCM to be awarded an R01 (from NHLBI). The parent grant uses the northern elephant seal as a model for evaluating the physiological and cellular mechanisms some mammals have evolved that have allowed them to naturally adapt to extreme environmental conditions such as prolonged fasting and apnea (both sleep- and diving- induced) that may promote oxidative stress and its related pathologies. These are conditions that would otherwise be detrimental and eventually fatal in humans. Goals. This award will allow me to expand my research program further by using the protected time to learn and incorporate technologies and skills that we have not used previously in the lab such as qRT-PCR and advanced chromatography. While we have begun to explore these techniques, the protected time will allow me to focus more time on getting these techniques implemented as stable and routine methodologies in the lab. This will expand our capabilities and improve the overall quality of our science. Improving our science will ultimately increase our productivity and thus greatly enhance my chances of obtaining tenure, which is my relatively near-term (within the next 1-2 yrs) goal. Ultimately, my goal within the next 2-3 years is to have sufficient research support in the form of multiple and concurrent R-level awards for the remainder of my career. This level of funding should be sufficient to support a research team at least 10 members that is capable of producing 4-5 papers per year. Once I have fully established my research career and the requisite skills and techniques in my lab, I intend to develop and direct extramurally-funded training programs (such as MHIRT, MBRS and MARC) for underrepresented minorities as I continue my biomedical research. I consider my self a product of these programs having been involved with them since I was an undergraduate at Texas A&M and I currently participate in the UCSC-MHIRT program, which has given me extensive experience with such programs. Environment. My lab and that of my collaborators (mentioned in parent R01 grant) have all the space and equipment to required to accomplish the scientific goals of the proposed studies. I have 3 senior colleagues collaborating with me on the parent grant that I meet with regularly to discuss the progress of the grant. In turn, they provide extended mentorship and research direction to help insure my weaning to full research independence. The protected time will also enhance the training of my students I will be able to commit more time to supervising their research that is supported by the parent grant. Research. The goal of this newly proposed specific aim is to evaluate the contributions of purine recycling and HIF-1 activation to the northern elephant seal's natural tolerance against sleep apnea-induced hypoxia.
This specific aim will address the hypothesis that elephant seals avoid potential free radical production by recycling purine nucleosides derived from sleep apnea- induced hypoxia, and that HIF-1 is activated by redox-dependent mechanisms during sleep apnea in order to coordinate the cellular homeostatic response against hypoxia.
Ortiz, Rudy M. K02: Independent Scientist Award Project Narative Elephant seals experience prolonged periods of food and water deprivation in addition to chronic sleep apnea-induced hypoxia, both of which can rapidly evoke cardiovascular and respiratory complications in humans. However, these seals must have evolved uniquely robust physiological and cellular mechanisms to counter the potentially detrimental consequences commonly associated with these behaviors. Elucidation of these mechanisms in seals may reveal novel therapeutic targets to help alleviate these consequences in humans. The proposed studies provide the initial steps towards developing the northern elephant seal as a viable biomedical model to study the natural adaptations evolved to counter oxidative stress and inflammatory events commonly induced by prolonged food deprivation and, sleep- and diving-associated hypoxia.
|Martinez, Bridget; SoÃ±anez-Organis, JosÃ© G; Viscarra, Jose A et al. (2016) Glucose delays the insulin-induced increase in thyroid hormone-mediated signaling in adipose of prolong-fasted elephant seal pups. Am J Physiol Regul Integr Comp Physiol 310:R502-12|
|Suzuki, Miwa; Lee, Andrew Y; VÃ¡zquez-Medina, JosÃ© Pablo et al. (2015) Plasma FGF21 concentrations, adipose fibroblast growth factor receptor-1 and Î²-klotho expression decrease with fasting in northern elephant seals. Gen Comp Endocrinol 216:86-9|
|Minas, Jacqueline N; Thorwald, Max A; Conte, Debra et al. (2015) Angiotensin and mineralocorticoid receptor antagonism attenuates cardiac oxidative stress in angiotensin II-infused rats. Clin Exp Pharmacol Physiol 42:1178-88|
|Suzuki, Miwa; VÃ¡zquez-Medina, JosÃ© Pablo; Viscarra, Jose A et al. (2013) Activation of systemic, but not local, renin-angiotensin system is associated with upregulation of TNF-Î± during prolonged fasting in northern elephant seal pups. J Exp Biol 216:3215-21|
|Viscarra, Jose Abraham; Ortiz, Rudy Martin (2013) Cellular mechanisms regulating fuel metabolism in mammals: role of adipose tissue and lipids during prolonged food deprivation. Metabolism 62:889-97|
|VÃ¡zquez-Medina, JosÃ© Pablo; Popovich, Irina; Thorwald, Max A et al. (2013) Angiotensin receptor-mediated oxidative stress is associated with impaired cardiac redox signaling and mitochondrial function in insulin-resistant rats. Am J Physiol Heart Circ Physiol 305:H599-607|
|Martinez, Bridget; SoÃ±anez-Organis, JosÃ© G; VÃ¡zquez-Medina, JosÃ© Pablo et al. (2013) Prolonged food deprivation increases mRNA expression of deiodinase 1 and 2, and thyroid hormone receptor Î²-1 in a fasting-adapted mammal. J Exp Biol 216:4647-54|
|Viscarra, Jose A; Rodriguez, Ruben; Vazquez-Medina, Jose Pablo et al. (2013) Insulin and GLP-1 infusions demonstrate the onset of adipose-specific insulin resistance in a large fasting mammal: potential glucogenic role for GLP-1. Physiol Rep 1:e00023|
|SoÃ±anez-Organis, JosÃ© G; VÃ¡zquez-Medina, JosÃ© P; Crocker, Daniel E et al. (2013) Prolonged fasting activates hypoxia inducible factors-1Î±, -2Î± and -3Î± in a tissue-specific manner in northern elephant seal pups. Gene 526:155-63|
|VÃ¡zquez-Medina, JosÃ© Pablo; SoÃ±anez-Organis, JosÃ© G; Rodriguez, Ruben et al. (2013) Prolonged fasting activates Nrf2 in post-weaned elephant seals. J Exp Biol 216:2870-8|
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