Nicholas Khoo, PhD

Research Assistant Professor

E1314 Thomas E. Starzl Biomedical Science Tower
200 Lothrop Street
Pittsburgh, PA 15261
Phone: 412-648-9671
Fax: 412-648-2229

Education

B.A. (Biology), University of Iowa, 1996
Ph.D. (Free Radical and Radiation Biology), University of Iowa, 2003
Nicholas Khoo, PhD
Link:  Translational Program Project / Vascular Sub-Phenotypes of Lung Disease  http://www.vmi.pitt.edu/tPPG.html 
 
  1. Define the formation and signaling actions of electrophilic nitro-fatty acids. Electrophilic nitroalkene-containing fatty acids (NO2-FA) are products of nitric oxide (NO)/nitrogen dioxide reactions with unsaturated fatty acids that are generated at increased rates during metabolic stress and inflammation.  These endogenously produced mediators display a broad range of adaptive signaling actions. While the nitroalkene moiety confers reversible electrophilic reactivity with nucleophiles such as cysteine and histidine, promoting the post-translational modification of reactive protein thiols, the exact signaling mechanisms underlying the physiological actions of NO2-FA and their conditions of formation and metabolism remain unclear.
  2. Determining the interplay between mechanisms of adipose dysfunction and electrophilic nitro-fatty acid signaling to modulate obesity and insulin resistance. Obesity, a low-grade systemic inflammatory disease, is central to the pathogenesis of insulin resistance and type 2 diabetes. White adipose tissue, a major physiological compartment affected by obesity, has emerged as a signaling nexus that strongly impacts energy balance and glucose homeostasis. While our studies suggest that adipose tissue is a unique environment for NO2-FA signaling, the molecular mechanism(s) by which obesity impacts NO2-FA actions and those accounting for the therapeutic actions of NO2-FA remain unclear. Some of the publications listed below demonstrate the significant impact adipose tissue has on glucose homeostasis, the esterification process of NO2-FAs in adipocytes and that NO2-FAs improve glucose tolerance. 
  3. Define fundamental signaling mechanisms of tissue generation and reactions of reactive oxygen species (ROS). Oxidative stress, which occurs when ROS levels are higher than the antioxidant enzyme activities within a cell, is linked with a plethora of pathologies. However, ROS also have been described as signaling molecules that regulate physiological homeostasis. Assessment of reactive species in tissues and cells is routinely accomplished by measuring the accumulation of more stable secondary byproducts of redox reactions and/or the reduction in concentration of small molecule antioxidants (such as glutathione). Over the last few years we have published techniques to accurately detect reactive species in vivo (DMPO method), determine the source of oxidants from enzymes and the regulation of antioxidant enzymatic activities. These publications are seminal in defining conditions of oxidative stress in tissues and cells.
In summary, these research interests will generate insights into mechanisms leading to obesity and its associated myriad of health problems and/or diseases such as diabetes, atherosclerosis and other cardiovascular complications, which will hopefully elucidate novel preventative and therapeutic strategies.
Fazzari M, NK Khoo, SR Woodcock, L Li, BA Freeman and FJ Schopfer.  Generation and esterification of electrophilic fatty acid nitroalkenes in triacylglycerides.  Free Radic Biol Med 87:113-124, 2015.
Chartoumpekis DV, DL Palliyaguru, N Wakabayashi, NK Khoo, G Schoiswohl, RM O'Doherty and TW Kensler. Notch intracellular domain overexpression in adipocytes confers lipodystrophy in mice. Molecular Metabolism 4:543-550, 2015.
Kelley EE, J Baust, G Bonacci, F Golin-Bisello, JE Devlin, CM St Croix, SC Watkins, S Gor, N Cantu-Medellin, ER Weidert, JC Frisbee, MT Gladwin, HC Champion, BA Freeman and NK Khoo. Fatty acid nitroalkenes ameliorate glucose intolerance and pulmonary hypertension in high-fat diet-induced obesity. Cardiovasc Res 101:352-363, 2014.
Khoo NK, L  Mo, S Zharikov, C Kamga-Pride, K Quesnelle, F Golin-Bisello, L Li, Y Wang and S Shiva. Nitrite augments glucose uptake in adipocytes through the protein kinase A-dependent stimulation of mitochondrial fusion. Free Radic Biol Med 70:45-53, 2014.
Khoo NK, S Hebbar, W Zhao, SA Moore, FE Domann and ME Robbins. Differential activation of catalase expression and activity by PPAR agonists: Implications for astrocyte protection in anti-glioma therapy. Redox Biol 1:70-79, 2013. 
Khoo NKH, N Cantu-Medellin, JE Devlin, CM St Croix, SC Watkins, AM Fleming, HC Champion, RP Mason, BA Freeman and EE Kelley.  Obesity-induced tissue free radical generation:  An in vivo immuno-spin trapping study.  Free Radical Biol Med 52:2312-2319, 2012.
Khoo NKH, V Rudolph, MP Cole, F Golin-Bisello, SR Woodcock, C Batthyany and BA Freeman.  Activation of vascular endothelial nitric oxide synthase and heme oxygenase-1 by electrophilic nitro-fatty acids.  Free Radical Biology and Medicine 48:230-239, 2010.
Khoo NKH, CR White, L Pozzo-Miller, F Zhou, C Constance, T Inoue, RP Patel and DA Parks.  Dietary flavonoid quercetin stimulates vasorelaxation in aortic vessels.  Free Radical Biology and Medicine 49:339-447, 2010.

Sponsored Research

Characterizing nitro-fatty acids as Rad51 inhibitors as co-treatment in triple negative breast cancer - 2/1/2019 - 1/31/2022
DOD - BC1804671P1
Vascular Subphenotypes of Lung Disease (Proj. 2) - 8/1/2016 - 4/30/2021
NIH - P01HL103455
Anti-Inflammatory Lipid Mediators in Asthma - 8/5/2016 - 6/30/2020
NIH - R01 HL132550
(1) Assessment of 8,9-alkene and 10-nitrostearate effects on NF-kB signaling pathway and (2) Evaluation of Nrf2 activation by 10-nitrostearate and 8,9-alkene - 8/31/2018 - 8/30/2019
Complexa, Inc. - CRA