Dr Aseem Kumar

 

Professor

 

 

Ph.D. (University of Toronto)


Office: S-720

Labs: S-712, S-715

 

Mailing Address

Dr. A. Kumar
Department of Chemistry & Biochemistry
Laurentian University
Sudbury, ON
P3E 2C6

 

Telephone
(705) 675-1151, ext 2103, 2295

Fax
(705) 675-4844

 

Internet:

akumar@laurentian.ca

 

 

 

Identification and characterization of sepsis molecular signaling pathways


            Sepsis and septic shock represent the overwhelming response to infection. Approximately 800,000 cases of sepsis are admitted every year to hospitals in the North America and despite aggressive antibiotics and supportive care, over 200,000 patients per year succumb to this disorder. Sepsis and sepsis-associated multiple organ failure are the leading cause of death in intensive care units of the developed world and claim over 500,000 lives per year world wide. We are characterizing new initiators and mediators of sepsis and septic shock. These pathways and processes include: cytokine signalling, transcription factor modulation, apoptosis, bacterial DNA and RNA signalling and characterization of global gene expression patterns that occur during the disease. To examine these signalling events we have developed a tissue culture model and a mouse model of sepsis and septic shock. We are also studying tissues from spontaneous human sepsis and septic shock.

Research Projects:

(1) Cytokine and transcription factor regulation: We are identifying infecting organism(s), cytokine profile (including IFNs, ILs and TNFs) and transcription factor profile (including STAT, IRF and NF-?B) in our models of sepsis. We are currently determining if modulation of these cytokines and transcription factors during the disease will increase viability.

(2) Apoptosis: We have shown that apoptosis occurs during sepsis and septic shock with an increase in caspase gene expression and activation. We are characterizing caspase gene family expression and are employing inhibitors of caspase activation as a drug therapy.

(3) Bacterial DNA and RNA: We have determined that bacterial DNA and RNA induce a depression of myocyte contraction. Regulation of the pathways involved in bacterial DNA and RNA dependent myocyte depression may lead to novel therapeutics.

(4) Global gene expression: We have determined that genes involved in the pro-inflammatory response, cell adhesion molecule regulation, apoptosis and cell cycle control are modulated during sepsis. We are using rationale drug design to alter deleterious gene expression patterns that occur during sepsis and septic shock.

Selected Publications

 

Farag Bleiblo, Paul Michael, Chilakamarti V. Ramana, TC Tai, Mazen Saleh, Joseph E. Parrillo, Anand Kumar and Aseem Kumar.  STAT1 and STAT2 Null Cells are Resistant to Bacterial RNA-Induced Apoptosis Due to a Deficiency in the Consititutive and Inducible Activation of Apoptosis-Regulating Proteins. Manuscript submitted.

 

Farag Bleiblo, Paul Michael, Danielle Brabant,  Chilakamarti V. Ramana, TC Tai, Mazen Saleh, 

Joseph E. Parrillo, Anand Kumar and Aseem Kumar.  Janus Kinases are Required for the RNA-Induced Tyrosine Phosphorylation of PKR. Manuscript submitted.

                                                                                                                                                          

Emily Rimmer, Anand Kumar, Steve Doucette, Ryan Zarychanski and The Co-operative

Antimicrobial Therapy of Septic Shock (CATSS) Database Research Group (Aseem Kumar is a member of this group). Act. Prot. C and Septic Shock: A Propensity-Matched Cohort Study.Manuscript submitted.

 

Yaseen Arabi, Saqib Dara, Ziad Memish Abdulmajeed Al-Abdulkareem, Hani M. Tamim, Nehad Al- Shirawi, Joseph E. Parrillo, Stephen Lapinski, Daniel Feinstein, Gordon Wood, Sandra Dial, Anand  Kumar and The Cooperative Antimicrobial Therapy of Septic Shock (CATSS) Database Research Group (Aseem Kumar is a member of this group). Antimicrobial Therapeutic Determinants of Outcomes in Patients with Cirrhosis-Associated Septic Shock.  Manuscript submitted.

 

 Manish Sood, Anand Kumar and the Cooperative Antimicrobial Therapy in Septic Shock (CATSS) Database Research Group (Aseem Kumar is a member of this group). Reversible AKI in Early Septic Shock is Associated with Improved Survival. Manuscript submitted.

 

Farag Bleiblo, Paul Michael, Danielle Brabant,  Chilakamarti V. Ramana, TC Tai, Mazen Saleh, Joseph E. Parrillo, Anand Kumar and Aseem Kumar.  Bacterial RNA Induces Myocyte Cellular Dysfunction through the Activation of PKR. In Press, J. Thoracic Disease. January 2012.

 

Farag Beliblo, Paul Michael, Danielle Brabant, Chilakamarti V. Ramana, TC Tai, Mazen Saleh, Joseph E. Parrillo, Anand Kumar and Aseem Kumar. The Role of Immunostimulatory Nucleic Acids in Septic Shock. International Journal of Clinical and Experimental Medicine, 5(1) 1-23,  2012.

 

Ismail Cinel, Mustafa Ark, Phillip Dellinger, Tuba Karabacak, Lulufer Tamer, Leyla Cinel,

Paul Michael, Shaimaa Hussein, Joseph E. Parrillo, Anand Kumar and Aseem Kumar.

Involvement of Rho kinase (ROCK) in Lung Injury Induced by Cecal Ligation and Puncture (CLP). Featured Article in J. Thoracic Disease with two editorials. 4, No 1, 30-39, 2012.

 

Danielle Brabant, Paul Michael, Ravin Narain, Mazen Saleh, Anand Kumar, Joseph E. Parrillo

and Aseem Kumar. Sepsis Mediated Cellular Dysfunction is Mediated by DFF 40 Induced

Apoptosis. Biochemical and Biophysical Research Communications. 412, 260-265, 2011.

 

James Crispo, Dominique Ansell, Mathew Piche, Joseph Eibl, Isabella Tai, Aseem Kumar, 

Gregory Ross and T.C. Tai. Protective Effects of Methyl Gallate on H2O2-induced Apoptosis in PC12 Cells. Biochemical and Biophysical Research Communications.  393, 773-778, 2010.

 

Marya Ahmed, Zhicheng Deng, Shiyong Deng, Aseem Kumar and Ravin Narain. Cationic

Glyconanoparticles: Complexation with DNA and Their Cellular Uptake.  Bioconjugate

 Chemistry.  20(11), 2169-2176, 2009.

 

Chilakamarti V. Ramana, Guang-Shing Cheng, Aseem Kumar, H.J. Kwon and Richard

 Enelow. Alveolar Epithelial Early Growth Response-1 (EGR-1) Expression Triggered by

 Activated CD8+ T Cells is Critical for Chemokine Gene Expression and Lung Injury. Molecular Immunology. 47, Issues 2-3, 623-631, 2009.

 

Anand Kumar, Pau Ellis, Yaseen Arabi, Dan Roberts, Bruce Light, Joseph E. Parrillo, Peter

 Dodek, Gordon Wood, Aseem Kumar, David Simon, Cheryl Peters, Muhammad Ahasan, Dan Chateau. Initiation of Inappropriate Antimicrobial Therapy Results in a 5-fold Reduction of Survival in Human Septic Shock. Chest.  136, 1237-1248, 2009.

 

Shaimaa Hussein, Paul Michael, Amadeo Parissenti, Abdelwahab Omri, Anand Kumar, Joseph E. Parrillo and Aseem Kumar. Late Stage Bacterial Sepsis Induced Gene Profiling. International  Journal of Clinical and Experimental Medicine. 2(2), 131-148, 2009.      

                              

Bagshaw, S.M. etal. (and the Cooperative Antimicrobial Therapy of Septic Shock (CATSS)

Database Research Group (Aseem Kumar is a member of this group). Acute Kidney Injury in Septic Shock: Clinical Outcomes and Impact of Duration of Hypotension Prior to Initiation of Antimicrobial Therapy.  Intensive Care Medicine. 35, 871-881, 2009.

 

 Catherine Song, Aseem Kumar, Abdel Omri and Mazen Saleh. Bioinformatics Comparison of

 Bacterial Secretomes. Genomics, Proteomics and Bioinformatics. 7, 25-36, 2009.

 

Anand Kumar and Aseem Kumar. Sepsis and Septic Shock. Editors: A. Gabrielli, J. Layon and

 M. Yu. Civetta, Taylor and Kirby's Critical Care 4th Ed. June 2009.          

 

Kumar Anand, Kumar Aseem, Parrillo JE: Myocardial Dysfunction in Sepsis and Septic Shock.

 Acute Heart Failure Sydnromes: A Practical Approach for Physicians. Editor: Alexandre

 Mebazaa. Springer-Verlag. June 2008.         

                                                                                                                                               

Rama Kota, Ramana Chilakamarti and Aseem Kumar. Lipoprotein Lipase in Atherosclerosis.     

Recent Developments in Signal Transduction Research. Research Signpost, Editor: R. V.

Chilakamarti May 2008.

 

Ramana Chilakamarti, Rama Kota and Aseem Kumar. CD8+ T-cell Recognition and Lung

Injury. Recent Developments in Signal Transduction Research. Research Signpost, Editor: R. V.

Chilakamarti May 2008.        

 

Majed Halwani, Shanna Blomme, Zacharias E. Suntres, Misagh Alipour, Ali O. Azghani,

 Aseem Kumar and Abdelwahab Omri. Liposomal Bismuth-Ethanedithiol Formulation Enhances

 Antimicrobial Activity of Tobramycin. International Journal of Pharmaceutics, 358, 278-284,    

 2008.

 

Marisa Tessier, Paul Michael, Danielle Brabant,  Ramana V. Chilakamarti, Abdel Omri, Mazen 

 Saleh, Joseph E. Parrillo, Anand Kumar and Aseem Kumar. Characterization of Factors in Human

 Septic Sera that Mediate Cellular Dysfunction.. Recent Developments in Signal Transduction  

 Research. Research Signpost, (refereed paper with original data published as a book chapter)  Editors:

 Ramana V. Chilakamarti, pages 1-23, May 2008.

 

Lisa Falvo, Paul Michael, Xiulong Xu, Joseph E. Parrillo, Abdelwahab Omri, Anand Kumar and

Aseem Kumar. Human Septic Serum Induced Apoptotic Gene Expression Profile in Human

Myocytes. Cell Apoptosis Research Progress, (refereed paper with original data published as a book

chapter) Nova Publishing, Editor: Robert H. Fenton, pages 135-152, May 2008.

 

Kumar Anand and Kumar Aseem: Development of Sepsis Therapeutics and Molecular           

Diagnostics. Expert Commentary, Nova Publishing 2008.

 

Majed Halwani, Clement Mugabe, Ali O. Azghani, Robert M. Lafrenie, Aseem Kumar and

Abdelwahab Omri. Bactericidal Efficacy of Liposomal Aminoglycosides against Burkholderia

Cenocepacia. Journal of Antimicrobial Chemotherapy, 60:760-769, October 2007.

 

Danielle Brabant, Paul Michael, Chilakamarti V. Ramana, Joseph E. Parrillo, Anand Kumar and

Aseem Kumar. Characterization of Key Apoptotic Signalling Pathways that Mediate Sepsis

Induced Cellular Dysfunction, New Cell Apoptosis Research (refereed paper with original data

published as a book chapter at Nova Publishing, Editor. C. Pickens) pages 1-40, July 2007.

 

Anand Kumar, Bhanu Paladugu, Joel Mensing, Aseem Kumar and Joseph E. Parrillo.  Nitric

Oxide-Dependent and -Independent Mechanisms are Involved in TNF-a-Induced Depression

 of Cardiac Myocyte Contractility. American Journal of Physiology 292:1900-1906, 2007.

 

Anand Kumar, Aseem Kumar, Bhanu Paladugu, Joel Mensing and Joseph E. Parrillo. 

 TGF-b Blocks in-vitro Cardiac Myocyte Depression Induced by TNF-a and IL-1b and Human

 Septic Shock Serum. Featured Article Critical Care Medicine Journal 35:358-364, 2007.

 

 Rama S. Kota, Kapilchandra Gohil, Aseem Kumar , Richard  I. Enelow, John C. Rutledge  and  

 Chilakamarti.V. Ramana. Regulation of gene expression in RAW 264.7 macrophages by

 Interferon-gamma. Biochemical and Biophysical Research Communications 342:1137-1146, 2006.

 

Anand Kumar, Kenneth E. Wood, Robert Suppes, Joseph E. Parrillo, Daniel Feinstein,        

Satendra Sharma, Sergio Zanotti, Leo Taiberg, David Gurka, Aseem Kumar, Mary Cheang,

Bruce Light, Daniel Roberts. Duration of Hypotension Prior to Initiation of Effective  

Antimicrobial Therapy is the Critical Determinant of Survival in Human Septic Shock.           Featured Article in Critical Care Medicine Journal 34:1589-1596, 2006.

 

Anand Kumar, Bhanu Paladugu, Cameron Haery, Aseem Kumar, Simon Symeoneides,

Gordon Trenholme, Joanne Sandelski, Steve Opal and Joseph E. Parrillo. Duration of

Hypotention Prior to Antibiotic Administration is a Critical Determinant of Outcome in a

Murine Model of E. coli Septic Shock.

Major Article in the Journal of Infectious Diseases 193:251-258, 2006.

 

M. Pilar Gil, Aseem Kumar, Richard I. Enelow and Chilakamarti V. Ramana.  STAT1-

 independent Pathways in Interferon Signaling. Interferons (editor Kailash Chadha, Roswell Park

Cancer Center, Buffalo, NY) 2006.

 

Aseem Kumar, Anand Kumar, Xiulong Xu and Joseph E. Parrillo.

Human Serum Derived from Patients with Septic Shock Activates Transcription Factors  

STAT1, IRF1, NF-kB and Induces Apoptosis in Human Cardiac Myocytes.

J. Biol. Chem. 280:42619-42626, Dec. 2005.

 

Chilakamarti V. Ramana, Aseem Kumar and Richard Enlow.  STAT1-independent Induction

of SOCS-3 by Interferon-g is Mediated by Activated STAT3 in Mouse Embryo Fibroblasts.

Biochemical and Biophysical Research Communications 327:727-733, 2005.

 

Kumar Anand, and Kumar Aseem: Nitric oxide and inflammatory cytokines in the heart:

The presence of positive feedback loops. Critical Care Medicine, 33:2851-2852, 2005.

 

Danielle Brabant, Paul Michael, Marija Tonnos, Marisa Tessier, Shuhung Kung, Anand Kumar,

Chilakamarti V. Ramana and Aseem Kumar.  Molecular Biology of Sepsis. Proceedings of the

International Biotechnology Symposia.  Haldia Institute of Technology, India, January 2005.

                                                                                                                                                        

Chilakamarti V. Ramana, Aseem Kumar, Jyothi Chinthrapalli and Richard I. Enelow.  CD8+ T

Cell and Alveolar Epithelial Cell Interactions in Lung Injury.  Proceedings of the International

Biotechnology Symposia.  Haldia Institute of Technology, India, January 2005.

 

Bhanu Paladugu, Anand Kumar, Joseph E. Parrillo, Sandy Der, Jailan Osman,

 Joel Mensing, Lisa Falvo, Xiulong Xu and Aseem Kumar.  Bacterial DNA and RNA Induce

 Rat Cardiac Myocyte Contraction Depression In-Vitro.

 Shock Journal 21(4):364-369, April 2004.

 

Kumar Anand and Kumar Aseem: Endotoxemic myocardial depression: A novel iNOS

suppressing effect of albumin. Critical Care Medicine, 31:324-326, 2003.

 

Ping Jiang, Aseem Kumar, Joseph E. Parrillo, Laurie A. Dempsey, Jeffrey L. Platt,               

Richard A. Prinz, Xiulong Xu. Transcriptional regulation of heparanase 1 gene

expression in thyroid neoplastic cell lines by Sp1.                                         

J. Biol. Chem.  277: 8989-8998,  March 15, 2002.    

 

Aseem Kumar, Anand Kumar and Joseph E. Parrillo.  IL-1 Gene Cluster: All in the

Family. Critical Care Medicine, 30:1168-1169, 2002.

                                                                                                                                               

Anand Kumar, Aseem Kumar and Joseph E. Parrillo.  Reversible Myocardial

Dysfunction: A Ubiquitous Phenomena in the Critically Ill? Critical Care Medicine,

30:1392-1393, 2002.

                                                                                                                                                       

Zanotti S, Kumar Aseem, Kumar Anand: Experimental and emerging therapies for

sepsis and septic shock: Part 2. Cytokine modulation in sepsis and septic shock.  

Expert Opinion in Investigational Drugs, 11:1061-1075, 2002.

                                                                                                                                                           

Manocha S, Feinstein D, Kumar Aseem, Kumar Anand: Experimental and emerging

therapies for sepsis and septic shock: Part 3. Anti-endotoxin strategies in gram-negative

sepsis and septic shock. Expert Opinion in Investigational Drugs, 11:1795-1812, 2002.

 

Krishnagopalan S, Kumar Aseem, Parrillo JE, Kumar Anand: Myocardial dysfunction

in sepsis and septic shock. Current Opinion in Critical Care, 5:376-388, 2002.

Court O, Kumar Aseem, Parrillo JE, Kumar Anand: Myocardial dysfunction in the

septic patient. Critical Care Medicine, 6:500-508, 2002.

 

Anand Kumar, Ana Krieger, Simon Symeoneides, Aseem Kumar and Joseph E. Parrillo. 

Myocardial Dysfunction in Septic Shock: Part II. Roles of Cytokines and Nitric Oxide.

Journal of Cardiothoracic and Vascular Anesthesia, Vol 15, No 4 (August), 2001: pp 485-511.

 

Xiao Rui Li, Anita Chong, Jianming Wu, Kenneth A. Roebuck, Aseem Kumar,

 Joseph E. Parrillo, Ulf R. Rapp, Robert P. Kimberly, James W. Williams and Xiulong

Xu.  Transcriptional Regulation of Fas Gene Expression by GA Binding Protein

(GABP) and AP1 in T Cell Antigen Receptor (TCR)/CD3 Complex-Stimulated T Cells.

 J. Biol. Chem.  274, 35203-35210, December 3, 1999.

 

Anand Kumar, Aseem Kumar and Joseph E. Parrillo. Cytokines and Septic Myocardial   

Depression:  Nitric Oxide vs. Sphingosine/Ceramide? Critical Care Medicine, 27:1391-

1393, 1999.

 

Aseem Kumar, Anand Kumar, G Skorupa, M Vukonich, B Paladugu,  P Narang,

C.Haery, H. Merchant and J E Parrillo.Characterzation Of Intracellular Signalling 

Components Involved in Sepsis. Nature  Biotechnology Short Reports, Volume 10 : 

Advances in Gene Technology; Signal transduction & therapeutic strategies, 1999;10:74   

                                                                                                                                                

Kumar Anand, Kumar Aseem, G Skorupa, Vukonich M, Paladugu B, Saleem A,

Narang P, Parvathala P, R Battula, R Makkena, Haery C, And Parrillo JE. Early human

septic serum-induced cardiac myocyte depression is caused by synergestic stimulation

of a constitutive nitric oxide synthase by TNF-Alpha and IL-1Beta

 Nature Biotechnology Short  Reports, Volume 10: Advances in Gene Technology ;

 Signal transduction and therapeutic strategies,1999;10:39.             

 

Aseem Kumar, Mairead Commane, Thomas Flickinger, Curt Horbath, and George R.

Stark.  Defective TNF-a-Induced Apoptosis in STAT1-Null Cells Due to Low

Constitutive Levels of Caspases.   

Science, 278, 1630-1632, November 28, 1997.

News and Views, 1541, ibid.

Perspective, 1578-1579, ibid.

 

Aseem Kumar, Yi-li Yang, Vincenzo Flati, Sandy Der, Suzanne Kadereit, Jaharul                 

Haque, Amitabha Deb, Luiz Reis, Charles Weissmann and Bryan R.G. Williams.

Deficient Cytokine Signalling in Mouse Embryo Fibroblasts with a Targeted Deletion

in the PKR Gene.                                                                                                                               

EMBO J. 16, 406-416, January 15, 1997.

 

Michael Rutherford, Aseem Kumar, Jaharul S. Haque and Bryan R.G. Williams. 

 Proto-oncogene Ets-1 Specifically Binds the ISRE of 2-5A Synthetase.  

 Journal of IFN and Cytokine Research 17, 1-10, 1997.                                                         

 [The first two authors contributed equally to the paper and should be considered as first 

 co-authors].

 

Michael Rutherford, Aseem Kumar, Benoit Coulombe, Dan Skup, Dave Carver and

 Bryan R.G. Williams.  Intracellular Interferon Constituitively Activates ISGF3 and

 Confers Resistance to EMC Viral Infection. 

 Journal of IFN and Cytokine Research 16, 507-510, July 1996.     

 [The first two authors contributed equally to the paper and should be considered as first co-authors].

 

Jaharul S. Haque, Heiko van der Kuip, Aseem Kumar, Walter E. Aulitzky, Michael N.

Rutherford, Christopher Huber,  Thomas Fischer, and Bryan R.G. Williams. Overexpression

of Mouse p140-Subunit of Replication Factor C Accelerates Cellular Proliferation.

Cell Growth and Differentiation 7,319-326, March 1996.                

 

Paul F. Torrence, Wei Xiao, Guiying Li, Shahrzad Khamnei, Krystyna Lesiak,                                   

Avudaiappan Maran, Ratan Maitra, Aseem Kumar, Beihua Dong, Bryan R. G. Williams

and Robert H. Silverman. Targeting RNA for Degradation with a (2',5')-oligoadenylate

Antisense Chimera.  Nucleosides and Nucleotides, 14(3-5), 1073-1076 (1995).                  

 

Yi-Li Yang, Luiz Reis, Jovin Pavlovic, Adriano Aguzzi, Reinhold Schafer, Aseem          

Kumar, Bryan R.G. Williams, Michel Auget and Charles Weissmann.  Deficient 

Signalling in Mice Devoid of Double-stranded RNA-dependent Protein Kinase, PKR.   

EMBO J. Vol. 14, no. 24, 6095-6106, December 15, 1995.

 

Cornelius F. Waller,M.D., Ratan K. Maitra, Ph.D., Avudaiappan Maran, Ph.D., Aseem

 Kumar, M.Sc., Beihua Dong, M.Sc., Wei Xiao, Ph.D., Guiying Li, Ph.D., Bryan R.G.

 Williams,Ph.D., Paul F. Torrence, Ph.D. and Robert H. Silverman, Ph.D.  2-5A-Anti-

 sense a Novel Approach to Cancer Therapy. Biology of Renal Cell Carcinoma,

 Springer-Verlag, 133-148 (1995).                                                     

 

A. Maran, R.K. Maitra, A.Kumar, B. Dong, W. Xiao, B.R.G. Williams, P.F. Torrence

and R.H. Silverman.  Blockage of NF-kB Signaling By Selective Ablation of an

mRNA Target by 2-5A-Antisense Chimeras. 

Science, Vol. 265, 789-792, August 5, 1994.

 

Aseem Kumar, Jaharul S. Haque, Judith Lacoste, John Hiscott and Bryan R.G.Williams. 

The dsRNA-Dependent Protein Kinase, PKR, Activates Transcription Factor NF-kB

by Phosphorylating IkB. 

Proc. Natl. Acad. Sci. USA, Vol. 91, 6288-6292, July 5, 1994.

 

Gengsheng Feng, Karen Chong, Aseem Kumar and Bryan R.G. Williams.

 Identification of dsRNA Binding Domains of the Interferon Induced Protein Kinase.

 Proc. Natl. Acad. Sci. USA, Vol. 89,5447-5451, June 1992.          

                                                                                               

Michael N. Rutherford, Aseem Kumar, Ahuva Nissim, Judith Chebath and Bryan

R.G. Williams. The Murine 2-5A Synthetase Locus:  Three Distinct Transcripts From

Two Linked Genes.  

Nucleic Acids Research, Vol. 19, 1917-1924, #8, 1991.

 

                                                                                                                                                                       

Book Editorships                                                                                                                               

 

Editors: Chilakamarti V. Ramana, Ph.D. and Aseem Kumar, Ph.D. Recent Developments in

Signal Transduction Research.  Research Signpost. May 2008. ISBN:978-81-308-0264-0

 
 
 
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