Nilofer Qureshi, Ph.D.

Professor, Director – Shock/Trauma Research Center, Director, Molecular & Cellular Immunology
Department(s) of Biomedical Sciences
Section: Microbiology
UMKC School of Medicine
816-235-1056
qureshin@umkc.edu
MG-CO5E
Education and Background

Ph.D. - Physiological Chemistry - University of Wisconsin

Meet Nilofer Qureshi
How did you become interested doing research?

My grandfather was a professor and director of a teaching hospital, and he treated patients free of charge. I wanted to become a doctor as well. Because I kept asking all of these questions, why does this happen, why does that happen, he finally said, “You should go into biomedical research where you can think, be creative and find out what’s really going on, and then determine mechanisms of drug action, and develop novel treatment strategies.”

What would you be doing today if not a medical researcher?

I would have gone into Foreign Service. My dad wanted me to because he was a commissioner (Taxation Service) and became chairman of an industrial development corporation. We used to attend a lot of parties and meet a lot of foreign dignitaries and VIP’s, so we had to behave, and be nice and polite. I can speak with anybody in the world and not be shy about meeting them.

What do you enjoy doing when you’re not working?

Research is fun at UMKC, but it is a 24-hour job. When I go home I have papers to read because I don’t have time during the day. I love to go boating on Lake Mendota (Madison) with my family. I also love to travel and have been to most of the cities in the United States, and to some of the big cities in Europe, and Russia. I love going to art and science museums, and enjoy painting, reading books, interior decoration, relaxing and listening to classical music to unwind.

Biography

Dr. Qureshi is a professor of biomedical science, and director of the Shock/Trauma Research Center. Trained at the University of Wisconsin/VA Medical Center, Dr. Qureshi focuses on basic/clinical research of novel treatments for sepsis based on the proteasomes. She is an internationally recognized expert in chemistry of toxins, antagonists for toxins, mechanisms responsible for septic shock and proteasomes.  Her research has been funded continually since 1994 by the National Institutes of Health as principal investigator. Her research program has fundamental relevance to basic science and translational research as evidenced by more than 160 peer-reviewed publications in scientific journals, and book chapters.

Dr. Qureshi has more than 35 years of experience in the fields of endotoxins and inflammation research, drug development, and translational research.  She has served as reviewer for professional scientific journals, and serves on the editorial board of the Shock journal and several other journals.  She has served as a reviewer for several national and international funding agencies including the National Institutes of Health and German agencies.

Dr. Qureshi was the first to establish the complete structure of the lipid A moiety of the enterobacterial lipopolysaccharide (LPS), developed monophosphoryl lipid A as an effective adjuvant; and Rhodobacter sphaeroides diphosphoryl lipid A as a powerful LPS antagonist in both in vitro and in vivo systems. Her recent research centers on the biology of LPS, especially, with regards to its effect on the ubiquitin-proteasome pathway in macrophages/monocytes and septic shock. Dr. Qureshi pioneered the concept that LPS-induced cytokines are dependent on the composition of proteasome’s subunits present in the cells. The proteasomes controls multiple signaling pathways triggered by LPS. All cells contain different subunits of proteasomes. The conclusion from these studies is that the proteasome is a central regulator of cellular function and inflammation/tolerance and is involved in several diseases such as septic shock, diabetes and cardiovascular problems, cancer and asthma. Presently, she is working on a novel therapeutic approach for septic shock based upon proteasome inhibitors / activators and antibiotics. Several important biomarkers present in blood of septic shock patients have been identified. Several natural compounds have now been developed for modulating the proteasome activities

Specialties and Research/Medical Interests

Biochemistry, Biomedical Informatics, Health Informatics, Cell Biology, Emergency Medicine

Research Focus

Sepsis and septic shock, diabetes, heart disease, cancer, and other diseases that are based on inflammatory processes.

An internationally recognized expert in physiological chemistry, biochemistry, molecular biology, and immunology, Qureshi’s focuses on pioneering studies of the structures of endotoxins, and mechanisms by which they act via the ubiquitin-proteasome pathway to cause disease. Her work has been continuously funded by the National Institutes of Health since 1994 and United States Department of Defense since 2005).

Research Summary

Dr. Qureshi was the first to establish the complete structure of the lipid A moiety of the enterobacterial lipopolysaccharide (LPS), developed monophosphoryl lipid A as an effective adjuvant; and Rhodobacter sphaeroides diphosphoryl lipid A as a powerful LPS antagonist in both in vitro and in vivo systems. Her recent research centers on the biology of LPS, especially, with regards to its effect on the ubiquitin-proteasome pathway in macrophages/monocytes and septic shock. Dr. Qureshi pioneered the concept that LPS-induced cytokines are dependent on the composition of proteasome’s subunits present in the cells. The proteasomes controls multiple signaling pathways triggered by LPS. All cells contain different subunits of proteasomes. The conclusion from these studies is that the proteasome is a central regulator of cellular function and inflammation/tolerance and is involved in several diseases such as septic shock, diabetes and cardiovascular problems, cancer and asthma. Presently, she is working on a novel therapeutic approach for septic shock based upon proteasome inhibitors / activators and antibiotics. Several important biomarkers present in blood of septic shock patients have been identified. Several natural compounds have now been developed for modulating the proteasome activities.

Selected Publications

Selected publications of more than 150

  1. Qureshi N, Takayama K, Heller D, Fenselau C: Position of ester groups in the lipid A backbone of lipopolysaccharides obtained from Salmonella typhimurium. J Biol Chem 258:12947-12951, 1983.
  2. Takayama K, Qureshi N, Mascagni P: Complete structure of lipid A obtained from the lipopolysaccharides of the heptose-less mutant of Salmonella typhimurium. J Biol Chem 258:12801-12803, 1983.
  3. Qureshi N, Mascagni P, Ribi E, Takayama K: Monophosphoryl lipid A obtained from lipopolysaccharides of Salmonella minnesota Purification of the dimethyl derivative by high performance liquid chromatography and complete structural determination. J Biol Chem 260:5271-5278, 1985.
  4. Raetz CRH, Purcell S, Meyer MV, Qureshi N, Takayama K: Isolation and characterization of eight lipid A precursors from a 3-deoxy-D-manno-octylosonic acid deficient mutant of Salmonella typhimurium. J Biol Chem 260:16080-16088, 1985.
  5. Strain SM, Armitage IM, Anderson L, Takayama K, Qureshi N, Raetz CRH: Location of polar substituents and fatty acyl chains on lipid A precursors from a 3-deoxy-D-manno-octylosonic acid -deficient mutant of Salmonella typhimurium. Studies by 1H, 13C, and 31P nuclear magnetic resonance. J Biol Chem 260: 16089-16098, 1985.
  6. Qureshi N, Cotter RJ, Takayama K: Application of fast atom bombardment mass spectrometry and nuclear magnetic resonance on the structural analysis of purified lipid A. J Microbiol Meth 5:65-77, 1986.
  7. Qureshi N, Honovich JP, Hara H, Cotter RJ, Takayama K: Location of fatty acids in Lipid A obtained from lipopolysaccharides of Rhodopseudomonas sphaeroides ATCC 17023. J Biol Chem 263: 5502-5504, 1988.
  8. Qureshi N, Takayama K, Mascagni P, Honovich J, Wong R, Cotter RJ: Complete structural determination of lipopolysaccharides obtained from deep rough mutant of Escherichia coli. Purification by high performance liquid chromatography and direct analysis by plasma desorption mass spectrometry. J Biol Chem 263: 11971-11976, 1988.
  9. Qureshi N, Takayama K, Meyer KC, Kirkland TN, Bush CA, Chen L, Wang R, Cotter RJ: Chemical reduction of 3-oxo and unsaturated groups in fatty acids of diphosphoryl lipid A from the lipopolysaccharide of Rhodopseudomonas sphaeroides. Comparison of biological properties before, and after reduction. J Biol Chem 266:6532-6538, 1991.
  10. Qureshi N, Takayama K, Kurtz R: Diphosphoryl lipid A obtained from the nontoxic lipopolysaccharide of Rhodopseudomonas sphaeroides is an endotoxin antagonist in mice. Infect Immun 59:441-444, 1991.
  11. Golenbock DT, Hampton RY, Qureshi N, Takayama K, Raetz CRH: Lipid A-like molecules that antagonize the effects of endotoxins on human monocytes. J Biol Chem 266:19490-19498, 1991.
  12. Baker PJ, Hraba T, Taylor CE, Myers KR, Takayama K, Qureshi N, Stuetz P, Kusumoto S, Hasegawa A: Structural features that influence the ability of lipid A and its analogs to abolish expression of suppressor T cell activity. Infect Immun 60:2694-2701, 1992..
  13. Qureshi N, Kaltashov, Walker K, Doroshenko V, Cotter RJ, Takayama K, Sievert TR, Rice PA, and Golenbock DT. Structure of the monophosphoryl lipid A moiety of lipopolysaccharide from Chlamydia trachomatis. J Biol Chem 272:10594-10600, 1997.
  14. Kirikae T, Kirikae F, Tominaga K, Qureshi N, Yamamoto S, and Nakano M. Rhodobacter sphaeroides diphosphoryl lipid A inhibits interleukin-6 production in CD14-negative murine marrow stromal cells stimulated with lipopolysaccharide or Paclitaxel (taxol). J Endotoxin Res 4:115-122, 1997.
  15. Qureshi N, Kutuzova G, Takayama K, Rice PA, and Golenbock DT. Structure of lipid A and cell activation. J Endotoxin Res 5:147-150, 1999.
  16. Lien E, Means TK, Heine H. Yoshimura A, Kusumoto S, Fukase K, Fenton MJ, Oikawa M, Qureshi N, Monks B, Finberg RW, Ingalls RR, and Golenbock DT. Toll-like receptor 4 imparts ligand-specific recognition of bacterial lipopolysaccharide. J Clin Invest 105:497-504, 2000.
  17. Kutuzova G, Albrecht R, Erickson C, and Qureshi N. Diphosphoryl lipid A from Rhodobacter sphaeroides blocks the binding and internalization of toxic lipopolysaccharide in RAW 264.7 cells. J Immunol 167:482-489, 2001.
  18. Jarvis BW, Harris TH, Qureshi N, and Splitter GA. Rough lipopolysaccharide from Brucella abortus and Escherichia coli differentially activates the same mitogen-activated protein kinase signaling pathways for tumor necrosis factor alpha in RAW 264.7 macrophage-like cells. Infection and Immunity 70:7165-7168, 2002.
  19. Qureshi N, Perera P-Y, Shen J, Zhang G, Lenschat A, Splitter G, Morrison DC, and Vogel SN. The proteasome as a LPS-binding protein in macrophages: Differential effects of proteasome inhibition on LPS-induced events. J Immunol. 171:1515-1525, 2003.
  20. Qureshi N, Vogel SN, Van Way III, Papasian C, Qureshi A, and Morrison DC. The proteasome, a central regulator of Inflammation and macrophage function. Immunologic Research 31/3:243-260, 2005.
  21. Shen J, Reis J, Morrison DC, Papasian C, Sreekumar R, Kolbert C, Qureshi A, Vogel SN and Qureshi N: Key Inflammatory signaling pathways are regulated by the proteasome. Shock 25:472-484, 2006.
  22. Shen J, Gao JJ, Zhang G, Tan X, Morrison DC, Papasian C, Vogel SN, and Qureshi N. Proteasome inhibitor, lactacystin blocks CpG DNA- and peptidoglycan induced inflammatory genes, cytokines and mitogen-activated protein kinases in macrophages. Shock 25: 594-599, 2006.
  23. Cole LE, Elkins K, Michalek SM, Qureshi N, Eaton LJ, Rallabhandi P, Cuesta N, and Vogel SN. Immunologic consequences of Francisella tularensis LVS infection: Role of innate immune response in infection and immunity. Immunol. 176:6888-6899, 2006.
  24. Yang R, Tan X, Thomas AM, Steppacher R, Qureshi N, Morrison DC, and Van Way, C, III. Alanine-glutamine dipeptide (AGD) inhibits expression of inflammation-related genes in hemorrhagic shock. JPEN 31:32-36, 2007.
  25. Reis J, Tan X, Yang R, Rockwell CE, Papasian CJ, Vogel SN, Morrison DC, Qureshi AA, and Qureshi N.   A combination of proteasome inhibitors and antibiotics prevents lethality in a septic shock model.  Innate Immunity 14: 319-329, 2008.
  26. Yang, R, Tan X, Kenney RJ Jr, Thomas AM, Landis M, Qureshi N, Morrison DC, and Van Way CW III.   Hemorrhagic Shock in the Rat: Comparison of Carotid and Femoral Cannulation. Journal of Surgical Research, 144:124-126, 2008.
  27. Rallabhandi P, Awomyl A, Thomas KE, Phalipon A, Fujimoto Y, Fukase K, Kusumoto S, Qureshi N,    Sztein MB, and Vogel SN.  Differential activation of human TLR4 by Escherichia coli and Shigella flexneiri 2a lipopolysaccharide: Combined effects of lipid A acylation state and TRL4 polymorphisms on signaling. Immunol 180:1139-1147, 2008.
  28. Rockwell CE, Morrison DC, and Qureshi N.  Lipid A-mediated tolerance and cancer therapy. Adv Exp Med Biol 2009; 667:81-99. Review.
  29. Cole LE, Yang Y, Elkins KL, Fernandez ET, Qureshi N, Shlomchik MJ, Herzenberg LA, Herzenberg LA, and Vogel SN. Antigen-specific B-1a antibodies induced by Francisella tularensis LPS provide long-term protection against tularensis LVS challenge. Proc Natl Acad Sci U S A. 2009 Mar 17; 106(11):4343-8. Epub 2009 Feb 26.
  30. Rockwell CE, and Qureshi N. Differential effects of lactacystin on cytokine production in activated Jurkat cells and murine splenocytes. Cytokine. 2010 Jul; 51(1):12-7. Epub 2010 Apr 27.
  31. Gao JJ, Shen J, Kohlbert C, Raghavaikaimal S, Papasian CJ, Qureshi AA, Vogel SN, Morrison DC, and Qureshi N. The proteasome regulates bacterial CpG DNA-induced signaling pathways in murine macrophages. Shock 34; 390-410, 2010.
  32. Yang R, Vernon K, Thomas A, Morrison D, Qureshi N, and Van Way CW. Crocetin reduces activation of hepatic apoptotic pathways and improves survival in experimental hemorrhagic shock. J Parenter Enteral Nutr 35:107-113, 2011.
  33. Reis J, Guan XQ, Kisselev AF, Papasian CJ, Qureshi AA, Morrison DC, Van Way CW 3rd, Vogel SN, Qureshi N. LPS-induced formation of immunoproteasomes: TNF-α and nitric oxide production are regulated by altered composition of proteasome-active sites. Cell Biochem Biophys. 60(1-2):77-88, 2011.
  34. Reis J, Hassan F, Guan XQ, Shen J, Monaco JJ, Papasian CJ, Qureshi AA, Van Way CW 3rd, Vogel SN, Morrison DC, Qureshi N. The immunoproteasomes regulate LPS-induced TRIF/TRAM signaling pathway in murine macrophages. Cell Biochem Biophys. 60(1-2):119-26, 2011.
  35. Beasley AS, Cotter RJ, Vogel SN, Inzana TJ, Qureshi AA, Qureshi N. A variety of novel lipid A structures obtained from Francisella tularensis live vaccine strain.  Innate Immun. 18(2):268-78, 2012. Epub 2011 Jun 27.
  36. Qureshi AA, Guan X-Q, Reis JC, Papasian CJ, Jabre S, Morrison DC, and Qureshi N. Inhibition of nitric oxide and inflammatory cytokines in LPS-stimulated murine macrophages by Resveratrol, a potent proteasome inhibitor.  Lipids in Health and Disease. 10; 11:76, 2012.
  37. Rockwell CE, Monaco JJ, and Qureshi N. A critical role for the inducible proteasomal subunits, LMP7 and MECL-1, in cytokine production by activated murine splenocytes. Pharmacology 89, 117-126, 2012
  38. Qureshi N, Morrison DC, and Reis J. Proteasome protease mediated regulation of cytokine induction and inflammation. Biophys. Acta. 1823: 2087-2093, 2012.
  39. Qureshi AA, Khan DA, Mahjabeen W, Papasian CJ, and Qureshi N. Nutritional supplement-5 with a combination of proteasome inhibitors (resveratrol, Quercetin, d-tocotrienol) modulate age-associated biomarkers and cardiovascular lipid parameters in human subjects. Clin Exp Cardiolog 4(3) 238, 2013.
  40. Wilks J., Lien E, ,Jacobson A., Fischbach MA, Qureshi N, Chervonsky AV and Golovkina TV.. Mammalian LPS receptors incorporated into the viral envelope augment virus infectivity. Cell, Host and Microbe 18::456-462,2015
  41. Qureshi AA*, Khan DA , Mahjabeen W, Trias MA , Silswal N and Qureshi N. Impact of δ-Tocotrienol on Inflammatory Biomarkers and Oxidative Stress in Hypercholesterolemic Subjects. J Clin. Exp Cardiolog. 6:367, 2015.
  42. Silswal N, Reis J, Qureshi AA, Papasian C, and Qureshi N. Of mice and Men: Proteasome’s role in LPS-induced Inflammation and Tolerance. Shock, Apr; 47(4):445-454, 2017.
  43. Qureshi AA, Reis JC, Badr MZ, Silswal N, and Qureshi N Selected compounds modulate various inflammatory biomarkers in lipopolysaccharide-induced macrophages of PPAR- J. Clin & Exp. Res.3 ISSN2394-6504, 2017.
  44. Silswal N, Reddy NS, Qureshi AA, Qureshi N. Resveratrol Downregulates Biomarkers of Sepsis via Inhibition of Proteasome’s Proteases. 2017 Dec 13. doi: 10.1097/SHK.0000000000001080. [Epub ahead of print]
  45. Qureshi N, Khan DA, Zuberi A, Vernon K, Kaja S, Drees BM, Qureshi AA, Van Way III CW, Morrison DC, and Silswal Internal Medicine Review, November 2017.