Dr. Alexzander A. A. Asea
Effie and Wofford Cain Centennial Chair in Clinical Pathology
Director, Division of Investigative Pathology
Director, Functional Proteomics Core Laboratory
Director for Research, Department of Pathology
Tenured Associate Professor of Pathology and Laboratory Medicine
Texas A&M Health Science Center College of Medicine, and Scott & White Memorial Hospital and Clinic
Phone: 254-743-0201
Fax: 254-743-0247
Email: asea@medicine.tamhsc.edu
aasea@swmail.sw.org

Education
1985 - B.Sc. (Honors), Biochemistry and Chemistry from Makerere University, Kampala, Uganda
1995 - Ph.D., Microbiology and Immunology from University of Göteborg, Göteborg, Sweden

Summary of Research Interests
Our long term goal is the research and development of heat shock protein-based therapies to be used alone or in combination with current therapies for the eradication of human diseases including cancer, diabetes and neurodegenerative disorders.

Our translational research programs are designed to further understanding of unique mechanisms by which heat shock protein-based drugs function. This is important because it is with this knowledge that we can develop even more potent drugs. In addition, we have preclinical tumor animal models and collaborate with clinician scientists in clinical trials.

Collaborations

Cancer stem cells (CSC) are cancer cells with characteristics associated with normal stem cells; more specifically they possess the ability to give rise to all cell types found in a particular cancer sample. It is thought that conventional chemotherapies kill differentiated or differentiating cells, which form the bulk of the tumor but are unable to kill new cells. However, CSC form a very small proportion of the primary tumor, which often remain unaffected by chemotherapy and cause a relapse of the disease. In collaboration with Dr. Sunil Krishnan (MD Anderson Cancer Center, Houston, TX) we are using gold nanoshell-mediated hyperthermia in combination with radiotherapy to completely eradicate CSC derived from breast, prostate and pancreatic cancers. 

Quercetin is a widely distributed bioflavonoid thought to act as a hyperthermia sensitizer in tumor cells by suppressing the expression of the seventy kilo-Dalton heat shock protein (Hsp72). However, the bioavailability of quercetin is very poor, and intravenous administration is necessary to establish efficient plasma concentrations of quercetin (PQC) in humans. In collaboration with Dr. Rűediger Wessalowski (University Children’s Hospital, Heinrich-Heine-University, Düsseldorf, Germany), successful intravenous application of quercetin in a 4-year-old girl with refractory sarcoma treated with combined thermo-chemotherapy. 

Current chemotherapeutic agents exhibit antitumor effects in a small number of cancers and adverse toxic effects in most of the patients. To overcome these problems, new antitumor agents are required. In this collaboration with Dr Susana Fiorentino (Universidad Javeriana, Bogotá, Colombia), we have identified a plant extract F4, derived from Petiveria alliacea L. (Phytolaccaceae), which has been used against leukemia and breast cancer with a lack of toxicity.

Adaptogens were initially defined as substances that enhance the “state of non-specific resistance” in stress, a physiological condition that is linked with various disorders of the neuroendocrine-immune system. The objective of our research with Drs Alexander Panossian and Georg Wikman (Swedish Herbal Institute, Vallberga, Sweden) is to identify the mechanism by which Hsp72 is involved in an adaptogen-induced stress response.

In the last decade alone, there has been an increase of 40% in the number of Americans diagnosed with diabetes. Over that same period, the obesity rate has also increased by nearly 20%. Therefore, efforts to identify any biomarker(s) to assist with obesity and diabetes prevention are of paramount importance. This study was designed to address the link between obesity and diabetes using proteomic analysis of drawn blood and collected urine samples. These studies are being performed in collaboration with Dr Samuel Forjuoh (Department of Family & Community Medicine, Texas A&M Health Science Center College of Medicine, Scott & White Memorial Hospital, Temple, TX).

Publications

• Kaur P, Asea A. The chaperokine activity of HspA1A. In Extracellular Heat Shock Proteins, eds. AG Pockley, B Henderson. Dordrecht, The Netherlands: Springer. 2012 (in press).
• Kaur P, Pradeep ANR, Asea A. Nucleolin: a novel intracellular transporter of HspA1A. In Extracellular Heat Shock Proteins, eds. AG Pockley, B Henderson. Dordrecht, The Netherlands: Springer. 2012 (in press).
• Campisi J, Sharkey C, Johnson JD, Asea A, Maslanik T, Bernstein-Hanley I, Fleshner M. 2012. Stress-induced facilitation of host response to bacterial challenge is dependent on extracellular Hsp72 and independent of α -T cells. Stress (in press).
• Panossian A, Kaur P, Wikman G, Asea A. 2012. Rhodiola rosea L. extract SHR-5 and salidroside stimulate neuropeptide Y expression in neuroglia cells. Frontiers in Neuroendocrine Science (in press).
• Nagaraja GM, Kaur P, Neumann W, Asea EE, Bausero MA, Multhoff G, Asea A. 2012. Silencing hsp25/hsp27 gene expression augments proteasome activity and increases CD8+ T cell-mediated tumor killing and memory responses. Cancer Prev Res (Phila). 5:122-137 (Figure featured on journal cover).
• Siepermann M, Koscielniak E, Dantonello T, Klee D, Boos J, Krefeld B, Borkhardt A, Hoehn T, Asea A, Wessalowski R. 2012. Oral low-dose chemotherapy: successful treatment of an alveolar rhabdomyosarcoma during pregnancy. Pediatric Blood and Cancer 58:104-106.
• Upreti M, Jamshidi-Parsian A, Koonce NA, Webber JS, Sharma SK, Asea AA, Mader MJ, Griffin RJ. 2011. Tumor-endothelial cell three-dimensional spheroids: new aspects to enhance radiation and drug therapeutics. Translational Oncology 4:365–376.
• Afroze SH, Uddin MN, Cao X, Asea A, Gizachew D. 2011. Internalization of exogenous ADP-ribosylation factor 6 (Arf6) proteins into cells. Mol. Cell Biochem Aug; 354(1-2):291-9. Epub 2011 Apr 27.
• Kaur P, Hurwitz MD, Krishnan S, Asea A. 2011. Combined hyperthermia and radiotherapy for the eradication of cancer. Cancers 3: 3799-3823.
• Kaur P, Asea A. 2011. Quantitation Methods for heat shock proteins in clinical samples using mass spectrometry. Meth Mol Biol 787:165-88.
• Kaur P, Nagaraja GM, Asea, A. 2011. Combined lentiviral and RNAi technologies for the delivery and permanent silencing of the hsp25 gene. Meth Mol Biol 787:121-36.
• Nagaraja GM, Kaur P, Zheng H, Bausero MA, Multhoff G, Asea A. 2011. Hsp25 is a repressor of PA28α and prohibitin: role in tumor growth and antigen presentation. Can. Preven. Res.
• Vareed SK, Bhat VB, Thompson C, Vasu VT, Fermin D, Hyungwon C, Creighton CJ, Gayatri S, Lan L, Putluri N, Thangjam GS, Kaur P, Shabahang M, Giri JG, Nesvizhskii AI, Asea A, Cashikar AG, Rao A, McLoughlin J, Sreekumar A. 2011. Metabolites of purine nucleoside phosphorylase (NP) in serum have the potential to delineate pancreatic adenocarcinoma. PLoS ONE 6:e17177.
• Siepermann M, Koscielniak E, Dantonello T, Klee D, Boos J, Krefeld B, Borkhardt A, Hoehn T, Asea A, Wessalowski R. 2011. Oral low-dose chemotherapy: successful treatment of an alveolar rhabdomyosarcoma during pregnancy. Pediatric Blood and Cancer Jan 16.
• Afroze SH, Uddin MN, Cao X, Asea A, Gizachew D. 2011. Internalization of exogenous ADP-ribosylation factor 6 (Arf6) proteins into cells. Mol. Cell Biochem. Apr 27.
• Kaur P, Asea A. 2011. Quantitation Methods for heat shock proteins in clinical samples using mass spectrometry. Meth. Mol. Biol.
• Zheng H, Nagaraja GM, Kaur P, Asea EE, Asea A. 2010. Chaperokine function of recombinant Hsp70 produced in insect cells using a baculovirus expression system is intact. J. Biol. Chem. 285(1): 349-356.
• Kaur P, Reis MD, Couchman GR, Forjuoh SN, Greene Jr JF, Asea A. 2010. SERPINE 1 Links Obesity and Diabetes: A Pilot Study. J. Proteomics Bioinform. 3: 191-199.
• Hurwitz MD, Kaur P, Nagaraja GM, Bausero MA, Asea A. 2010. Radiation therapy induces circulating serum Hsp72 in patients with prostate cancer. Radiother. & Oncol. Jun; 95(3): 350-8.
• Panossian A, Wikman G, Kaur P, Asea A. 2009. Adaptogens exert a stress-protective effect by modulation of expression of molecular chaperones. Phytomedicine 16: 617-622.
• Ortega E, Hinchado MD, Martin-Cordero L, Asea A. 2009. The effect of stress-inducible extracellular Hsp72 on human neutrophil chemotaxis: a role during acute intense exercise. Stress 12:240-249.
• Panossian A, Wikman G, Kaur P, Asea A. 2009. Adaptogens exert a stress-protective effect by modulation of expression of molecular chaperones. Phytomedicine 16:617-622.
• Asea A. 2008. Heat shock proteins and toll-like receptors. Handb. Exp. Pharmacol. 183:111-127.
• Asea A. 2008. Hsp70: a chaperokine. Novartis Found Symp. 291:173-179; discussion 179-183 and 221-174.
• Gross C, Holler E, Stangl S, Dickinson A, Pockley AG, Asea AA, Mallappa N, Multhoff G. 2008. An Hsp70 peptide initiates NK cell killing of leukemic blasts after stem cell transplantation. Leuk. Res. 32:527-534.
• Stangl S, Gross C, Pockley AG, Asea AA, Multhoff G. 2008. Influence of Hsp70 and HLA-E on the killing of leukemic blasts by cytokine/Hsp70 peptide-activated human natural killer (NK) cells. Cell Stress Chaperones 13:221-230.
• Asea A. 2007. Mechanisms of HSP72 release. J. Biosci. 32:579-584.
• Bausero MA, Bharti A, Page DT, Perez KD, Eng JW, Ordonez SL, Asea EE, Jantschitsch C, Kindas-Muegge I, Ciocca D, Asea A. 2006. Silencing the hsp25 gene eliminates migration capability of the highly metastatic murine 4T1 breast adenocarcinoma cell. Tumour Biol. 27:17-26.
• Svensson PA, Asea A, Englund MC, Bausero MA, Jernas M, Wiklund O, Ohlsson BG, Carlsson LM, Carlsson B. 2006. Major role of HSP70 as a paracrine inducer of cytokine production in human oxidized LDL treated macrophages. Atherosclerosis 185:32-38.
• Terry DF, Wyszynski DF, Nolan VG, Atzmon G, Schoenhofen EA, Pennington JY, Andersen SL, Wilcox MA, Farrer LA, Barzilai N, Baldwin CT, Asea A. 2006. Serum heat shock protein 70 level as a biomarker of exceptional longevity. Mech. Ageing Dev. 127:862-868.
• Asea A. 2005. Heat shock proteins and tumors. Modern Aspects in Immunol. 17:10-10.
• Bausero MA, Gastpar R, Multhoff G, Asea A. 2005. Alternative mechanism by which IFN-gamma enhances tumor recognition: active release of heat shock protein 72. J. Immunol. 175:2900-2912.
• Gastpar R, Gehrmann M, Bausero MA, Asea A, Gross C, Schroeder JA, Multhoff G. 2005. Heat shock protein 70 surface-positive tumor exosomes stimulate migratory and cytolytic activity of natural killer cells. Cancer Res. 65:5238-5247.
• Bausero MA, Page DT, Osinaga E, Asea A. 2004. Surface expression of Hsp25 and Hsp72 differentially regulates tumor growth and metastasis. Tumour Biol. 25:243-251.
• Terry DF, McCormick M, Andersen S, Pennington J, Schoenhofen E, Palaima E, Bausero M, Ogawa K, Perls TT, Asea A. 2004. Cardiovascular disease delay in centenarian offspring: role of heat shock proteins. Ann. N Y Acad. Sci. 1019:502-505.
• Barreto A, Gonzalez JM, Kabingu E, Asea A, Fiorentino S. 2003. Stress-induced release of HSC70 from human tumors. Cell Immunol. 222:97-104.
• Soncin F, Zhang X, Chu B, Wang X, Asea A, Ann Stevenson M, Sacks DB, Calderwood SK. 2003. Transcriptional activity and DNA binding of heat shock factor-1 involve phosphorylation on threonine 142 by CK2. Biochem. Biophys. Res. Commun. 303:700-706.
• Asea A, Rehli M, Kabingu E, Boch JA, Bare O, Auron PE, Stevenson MA, Calderwood SK. 2002. Novel signal transduction pathway utilized by extracellular HSP70: role of toll-like receptor (TLR) 2 and TLR4. J. Biol. Chem. 277:15028-15034.
• Calderwood SK, Asea A. 2002. Targeting HSP70-induced thermotolerance for design of thermal sensitizers. Int J Hyperthermia 18:597-608.
• Noessner E, Gastpar R, Milani V, Brandl A, Hutzler PJ, Kuppner MC, Roos M, Kremmer E, Asea A, Calderwood SK, Issels RD. 2002. Tumor-derived heat shock protein 70 peptide complexes are cross-presented by human dendritic cells. J. Immunol. 169:5424-5432.
• Asea A, Mallick R, Lechpammer S, Ara G, Teicher BA, Fiorentino S, Stevenson MA, Calderwood SK. 2001. Cyclooxygenase inhibitors are potent sensitizers of prostate tumours to hyperthermia and radiation. Int J Hyperthermia 17:401-414.
• Asea A, Kabingu E, Stevenson MA, Calderwood SK. 2000. HSP70 peptide-bearing and peptide-negative preparations act as chaperokines. Cell Stress & Chaperones 5:425-431.
• Asea A, Kraeft SK, Kurt-Jones EA, Stevenson MA, Chen LB, Finberg RW, Koo GC, Calderwood SK. 2000. HSP70 stimulates cytokine production through a CD14-dependant pathway, demonstrating its dual role as a chaperone and cytokine. Nature Medicine 6:435-442.