Professor and Vice Chair for Graduate Education
Assistant Dean of Graduate Studies
Ph.D. 1982, Indiana University
Specialty: Renal Physiology
Major Interest: Renal complications of type 1 diabetes; Contractile signaling in renal microvascular smooth muscle
Our studies utilize rodent models of type 1 diabetes (T1D) to elucidate mechanisms underlying the deleterious impact of this disease on renal function. Much of this work has focused on the causes and consequences of renal oxidative stress during T1D, revealing a role for oxidative stress in evoking T1D-induced renal arteriolar vasodilation (arising via effects on inward-rectifier K channels and calcium homeostasis) and accelerated sodium transport by the thick ascending limb (resulting from protein kinase C-mediated NADPH oxidase activation). Our work has implicated mitochondria as one source of renal reactive oxygen species during the early stage of T1D, a phenomenon associated with tyrosine nitration of key mitochondrial enzymes. Our recent efforts have unveiled a complex interplay between the full-length estrogen receptor α and its splice variants in modulating renal interstitial macrophage infiltration, glomerular hyperfiltration, glomerular enlargement and proteinuria during T1D. Working with our collaborators at the University of Alabama at Birmingham, we are currently exploring the endothelin-dependent underpinnings of endoplasmic reticulum (ER) stress in the kidney and the role of these processes in evoking the long-term renal consequences of T1D. This work may lay the groundwork for developing novel therapeutic approaches to prevent the onset and progression of diabetic nephropathy.
Dr. Carmines’ leadership role in Graduate Studies focuses on engagement and assessment. These efforts include leading the design team for Seguidor™ (UNMC’s Graduate and Postdoctoral Student Information System), providing career services and professional skills training for graduate students and postdoctoral fellows, and fostering partnerships with undergraduate institutions representing potential pipelines for future UNMC graduate students.
- De Miguel C, Hamrick WC, Hobbs JL, Pollock DM, Carmines PK, Pollock JS. Endothelin receptor-specific control of endoplasmic reticulum stress and apoptosis in the kidney. Sci Rep. 2017 Feb 23; 7:43152. doi:10.1038/srep43152. PMID:28230089
- Saleh MA, De Miguel C, Stevens DI, Carmines PK, Pollock DM, Pollock JS. Free radical scavenging decreases endothelin-1 excretion and glomerular albumin permeability during type 1 diabetes. Physiol Rep. 2016 Dec; 4(24). pii: e13055. doi:10.14814/phy2.13055. PMID:28039404
- Carmines PK. Mechanisms of altered renal microvascular function in type 1 diabetes: potential contribution to end organ damage. Curr Vasc Pharmacol. 2014;12(6):781-7. PMID:24066931
- Irsik D.L., Carmines PK., Lane P.H. Classical estrogen receptors and ERa splice variants in the mouse. PLoS One. 2013 Aug 5; 8(8):e70926. doi:10.1371/journal.pone.0070926. PMID:23940668
- De Miguel C., Foster JM., Carmines PK., Pollock JS. Interaction between NO synthase and NADPH oxidase in control of sodium transport by the renal thick ascending limb during diabetes. Acta Physiol (Oxf). 2013 Oct; 209(2):148-55. doi:10.1111/apha.12144. PMID:23841645