Neil Hogg, PhD
Professor; Associate Dean of Academic Affairs, Graduate School of Biomedical Sciences
PhD, Biological Chemistry, University of Essex, Colchester, England, 1993
MSc, Molecular Biochemistry, University of Essex, Colchester, England, 1989
BSc (honors), Biochemistry, University of Leeds, Leeds, England, 1987
- Anemia, Sickle Cell
- Nitric Oxide
- Nitric Oxide Donors
- Nitric Oxide Synthase
- Oxidative Stress
- Peroxynitrous Acid
- Reactive Nitrogen Species
Methodologies and Techniques
- Electron Spin Resonance Spectroscopy
- Nitric Oxide
- Reactive Nitrogen Species
- Assistant Dean for Recruitment, Graduate School
- Director, Biophysics Graduate Program
- Director, Redox Biology Program
Nitric Oxide Signaling
Nitric oxide (NO) is a free radical that is synthesized in biology by the nitric oxide synthase (NOS) family of enzymes. Though a plethora of literature describes the many, sometimes contradictory, effects of NO, much less known about the mechanisms by which these effects occur. Some molecular targets have been firmly established (such as the binding of NO to heme groups in guanylyl cyclase), whereas other potential targets for NO are less clearly defined. One major area of research in this laboratory is to elucidate the mechanisms by which NO and metabolites of NO interact with and modify protein targets to generate intracellular signals that can affect cellular function and potentially differential gene expression. We are conducting experiments to examine how NO transmits signals in cells using both global proteomic approaches and more directed approaches aimed at candidate proteins. Our ultimate goal is to define the mechanisms by which NO affects cellular functions at the level of individual protein modifications.
Sickle Cell Disease
Sickle cell disease (SCD) is one of the most known genetic diseases, and it has been established for many years that it is caused by a single amino acid mutation in the gene for the beta chain of hemoglobin. Despite its fame and prevalence (particularly in Africa and in populations of African descent), there is a pressing need for an increased understanding of this disease and for novel effective therapeutic approaches. SCD is characterized by hemoglobin polymerization in response to deoxygenation that results in distorted and rigid red blood cells, which may occlude vessels, leading to many of the features of this disease. However, it has become clear that simple blood vessel occlusion cannot explain many of the symptoms, and researchers are looking beyond the sickled RBC for clues to how this pathology progresses and how it can potentially be treated. New data relate many aspects of SCD pathology to intravascular hemolysis and an increase in plasma hemoglobin. This can interfere with normal nitric oxide-dependent vascular function and also potentially act as a pro-oxidant, leading to vascular dysfunction and altered endothelial adhesiveness. In collaboration with Drs. Cheryl Hillery and Nancy Wandersee in the Department of Pediatrics, we are conducting experiments to examine the role of intravascular hemolysis in SCD and in another hemolytic anemia, hereditary spherocytosis.
Nitrite as a Source of Nitric Oxide
While nitric oxide is mainly generated from L-arginine by nitric oxide synthase (NOS) enzymes, there is a growing realization that additional NO-generating pathways exist. The most common idea is that nitrite can be reduced back to NO via the nitrite reductase activity of some proteins and enzymes. While this is generally an activity that is associated with prokaryotes, several mammalian proteins and enzymes have currently been reported to have a low level nitrite reductase activity. These include xanthine oxidoreductase, cytochrome c oxidase, and, strangely enough, NOS itself. Interestingly, deoxygenated hemoglobin also possesses nitrite reductase activity (a fact realized as long ago as 1945), and it has recently been demonstrated that this activity represents a mechanism by which plasma nitrite can be converted back to vasoactive NO under deoxygenated conditions and so represents a hypoxically activated vasodilatory mechanism. We are currently studying the mechanisms of nitrite reduction and the role this plays in vascular pathology.
Past Graduate Students
Netanya Spencer (2003)
Yanhong Zhang (2004)
Kasia Broniowska (2008)
Nick Kettenhoffen (2009)
Timothy Flewelen (2013)
Zhen Ding (2013)
Ching-Fang Chang (2014)
(Keszler A, Lindemer B, Weihrauch D, Jones D, Hogg N, Lohr NL.) Free Radic Biol Med. 2019 02 01;131:443.
(Keszler A, Lindemer B, Hogg N, Lohr NL.) Redox Biol. 2019 01;20:13-18.
(van der Vliet A, Dick TP, Aust SD, Koppenol WH, Ursini F, Kettle AJ, Beckman JS, O'Donnell V, Darley-Usmar V, Lancaster J Jr, Hogg N, Davies KJA, Forman HJ, Janssen-Heininger YMW.) Free Radic Biol Med. 2018 08 20;124:353-357.
(Keszler A, Lindemer B, Hogg N, Weihrauch D, Lohr NL.) Arch Biochem Biophys. 2018 07 01;649:47-52.
(Keszler A, Lindemer B, Weihrauch D, Jones D, Hogg N, Lohr NL.) Free Radic Biol Med. 2017 12;113:157-164.
(Keszler A, Diers AR, Ding Z, Hogg N.) Nitric Oxide. 2017 05 01;65:1-9.
(Larson MC, Karafin MS, Hillery CA, Hogg N.) Transfus Med. 2017 Apr;27(2):136-141.
(Fahey JM, Emmer JV, Korytowski W, Hogg N, Girotti AW.) Photochem Photobiol. 2016 11;92(6):842-853.
(Oleson BJ, Broniowska KA, Naatz A, Hogg N, Tarakanova VL, Corbett JA.) Mol Cell Biol. 2016 08 01;36(15):2067-77.
(Wajih N, Liu X, Shetty P, Basu S, Wu H, Hogg N, Patel RP, Furdui CM, Kim-Shapiro DB.) Redox Biol. 2016 08;8:415-21.
(Kropp EM, Oleson BJ, Broniowska KA, Bhattacharya S, Chadwick AC, Diers AR, Hu Q, Sahoo D, Hogg N, Boheler KR, Corbett JA, Gundry RL.) Stem Cells Transl Med. 2015 May;4(5):483-93.
(Wandersee NJ, Maciaszek JL, Giger KM, Hanson MS, Zheng S, Guo Y, Mickelson B, Hillery CA, Lykotrafitis G, Low PS, Hogg N.) Blood Cells Mol Dis. 2015 Feb;54(2):183-8.