Chunhai (Charlie) Hao, MD, PhD

Neuropathology
Cancer Biology

Associate Professor
Pathology & Laboratory Medicine

Other Appointments/Positions

Member, Winship Cancer Institute, Emory University School of Medicine

Attending Pathologist (Neuropathology), Emory University Hospital

Pathology Division(s):
Anatomic Pathology
Experimental Pathology

Email Address:
chao@emory.edu

Education:

M.D.   Bei Hua University (Jilin Medical College), R. R. China, 1977 - 1982

M.Sc.   Jilin University (Norman Bethune University of Medical Sciences), China, 1983 - 1986

Ph.D.   University of Saskatchewan, Canada, 1986 - 1991

Residency of Neuropathology   University of Western Ontario, Canada, 1992 - 1997

Research Interests:

- TRAIL-induced apoptosis and cancer therapy
The goal of my research is to understand TRAIL physiology for the development of cancer therapeutic agents targeting TRAIL apoptotic pathways. TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) is normally expressed by natural killer cells and plays a role in anti-tumor immunity. TRAIL is therefore a natural cancer killer and recombinant TRAIL and its agonistic antibodies to its death receptors, DR4 and DR5 are currently in clinical trials for cancer therapies. The majority of human cancers, however, develop resistant mechanisms through activation of cell survival pathways. Recently we have identified the receptor-associated proteins complex and demonstrated that the proteins complex determines TRAIL-induced apoptotic and survival signal. Taking a proteomic approach, we have isolated and identified the proteins in the complex. The proteins identified in the complex include E3 ligases and substrate proteins modified by ubiquitin and SUMO (small ubiquitin-like modifier). Our current efforts therefore focus on (i) the characterization of the E3 ligases-mediated ubiquitination and SUMOylation of the substrate proteins in the complex, (ii) the investigation of how the ubiquitin and SUMO modifications modulate the interaction of the substrate proteins with their binding partners and thus control TRAIL-induced apoptotic and survival signaling, (iii) the development of small molecule inhibitors targeting of the ubiquitin/SUMO modification process, and (iv) the identification of the E3 ligases and/or their substrate proteins as biomarkers predicting the cancer responsiveness to TRAIL-based therapies. These research projects are currently funded by NIH R01 and grants from Georgia Cancer Coalition and Southeastern Brain Tumor Foundation.

Clinical Focus:

Diagnostic Neuropathology

Honors / Awards:

Georgia Cancer Coalition Distinguished Scholar, 2005 - 2010

Alberta Heritage Foundation for Medical Research Clinical Investigator, Canada, 2000-2004

Morrison H. Finlayson Award at the 33th and 35th Annual Meeting of Canadian Association of Neuropathologists (CANP), 1993, 1995

Specialty Boards:

1997 FRCPC Fellow of Royal College of Physicians & Surgeons of Canada

1997 Certificate in Neuropathology Royal College of Physicians and Surgeons of Canada

Selected Publications:

Published and Accepted Research Articles -

Chan CB, Abe M, Hashimoto N, Hao C, Williams IR, Liu X, Nakao S, Yamamoto A, Li SY, Hara-Nishimura I, Asano M, and Ye K. Mice Lacking asparagine endopeptidase develop disorders resembling hemophagocytic syndrome. Proc Natl Acad Sci U S A. 2009 Jan 13;106(2):468-73.

Bellail A, Tse MCL, Song JH, Phuphanich S, Olson JJ, Sun SY, Hao C. DR5-mediated DISC controls caspase-8 cleavage and initiation of apoptosis in human glioblastomas. J Cell Mol Med 2009 May 11; [Epub ahead of print]

Bellail A, Qing L, Mulligan P, Vaninder Chhabra and Hao C. TRAIL agonists on clinical trials for cancer therapy: the promises and the challenges. Rev Recent Clin Trials 2009 Jan; 4(1):34-41.

Wang P, Lo A, Young JB, Song JH, Lai R, Kneteman NM, Hao C*, Li L*. Targeted quantitative mass spectrometric identification of differentially expressed proteins between Bax-expressing and deficient colorectal cancer cells. *co-correspondents. J Proteome Res 2009 Jul; 8(7):3403-14.

Zarnitsyn VG, Meacham JM, Varady M, Hao C, Degertekin FL and Fedorov AG. Electrosonic ejector microarray for drug and gene delivery. Biomed Microdevices 2008;10(2):299-308.

Song JH, Tse MG, Bellail A, Khuri F, Phuphanich S, Kneteman NM and Hao C. Lipid rafts and non-rafts mediate TRAIL-induced apoptotic and non-apoptotic signals in non-small cell lung carcinoma cells. Cancer Res 2007; 67(14): 6946-55.

Liu X, Hu Y, Hao C, Rempel S and Ye K. PIKE-A is a proto-oncogene, promoting cell growth, transformation and invasion. Oncogene 2007; 26(34):4918-27.

Wang P, Zhang J, Bellail A, Jiang W, Hugh J, Kneteman NM and Hao C. Inhibition of RIP and c-FLIP enhances TRAIL-induced apoptosis in pancreatic cancer cells. Cell Signal 2007; 19:2237-46

Song JH, Bellail A, Tse MC, Yong VW and Hao C. Human astrocytes are resistant to Fas ligand and TRAIL-induced apoptosis. J Neurosci 2006;26(12):3299-308.

Wang CX, Song JH, Song DK, Yong VW, Shuaib A, and Hao C. Cyclin-dependent kinase-5 prevents neuronal apoptosis through ERK-mediated upregulation of Bcl-2. Cell Death Differ 2006; 13(7): 1203-12.

Wang P, Song JH, Song DK, Zhang J and Hao C. Role of death receptor and mitochondrial pathways in conventional chemotherapy drug induction of apoptosis. Cell Signal 2006; 18(9):1528-35.

Li YC, Tzeng CC, Song JH, Tsia FJ, Hsieh LJ, Liao SJ, Tsai CH, Van Meir EG, Hao C, and Lin CC. Genomic alterations in human malignant glioma cells associate with the cell resistance to the combination treatment with TRAIL and chemotherapy. Clin Cancer Res 2006;12(9):2716-29.

Xiao C, Yang BF, Song JH, Schulman H, Li L and Hao C. Inhibition of CaMKII-mediated c-FLIP expression sensitizes melanoma cells to TRAIL-induced apoptosis. Exp Cell Res 2005; 304 (1): 244-255

Alladina SJ, Song JH, Davidge ST, Hao C and Easton AS. TRAIL-Induced Apoptosis in Human Vascular Endothelium Is Regulated by Phosphatidylinositol 3-Kinase/Akt through the Short Form of Cellular FLIP and Bcl-2. J Vasc Res 2005; 42: 337-347

Camicioli R, Rajput A, Rajput M, Reece C, Payami H, and Hao C and Rajput A. Apolipoprotein E epsilon4 and catechol-O-methyltransferase alleles in autopsy-proven Parkinson's disease: Relationship to dementia and hallucinations. Mov Disord 2005; 20: 989-994.

Wang S, Tang H, Wilkinson V, Lukat T, Gelfand ET, Koshal A, Modry DL, Mullen JC, Hao C and Finegan BA. Saphenous vein harvest with SaphLITE system versus conventional technique: a prospective, randomized study. Ann Thorac Surg 2005; 79: 2018-2023

Song JH, Wang CX, Song DK, Wang P, Shuaib A and Hao C. Interferon g Induces Neurite Outgrowth by Up-regulation of p35 Neuron-specific Cyclin-dependent Kinase 5 Activator via Activation of ERK1/2 Pathway. J Biol Chem 2005; 280 (13): 12896-12901.

Sinclair DB, Aronyk K, Snyder T, McKean JD, Wheatley M, Gross D, Bastos A, Ahmed S N, Hao C and Colmers W. Extratemporal resection for childhood epilepsy. Pediatr Neurol 2004; 30 (3):177-85.

Roa W, Brasher PM, Bauman G, Anthes M, Bruera E, Chan A, Fisher B, Fulton D, Gulavita S, Hao C, Husain S, Murtha A, Petruk K, Stewart D, Tai P, Urtasun R, Cairncross JG and Forsyth P. Abbreviated course of radiation therapy in older patients with glioblastoma multiforme: a prospective randomized clinical trial. J Clin Oncol 2004 May 1; 22(9):1583-1588.

Hao C, Song JH, Hsi B, Lewis J, Song DK, Petruk KC, Tyrrell LJ and Kneteman NM. TRAIL inhibits tumor growth but is nontoxic to human hepatocytes in chimeric mice (Advances in Brief). Cancer Res (Highlights) 2004; 64:8502-8506.

Li Q, Dai Y, Guo L, Liu Y, Hao C, Wu G, Basora N, Michalak M and Chen X-Z. Polycystin-2 associates with tropomyosin-1, an actin microfilament component. J Mol Biol 2003; 325(5): 949-962.

Yang BF, Xiao C, Roa WH, Krammer PH and Hao C. Calcium/calmodulin-dependent protein kinase II regulation of c-FLIP expression and phosphorylation in modulation of Fas-mediated signaling in malignant glioma cells. J Biol Chem 2003; 278 (9): 7043-7050.

Sinclair DB, Aronyk K, Snyder T, McKean J, Wheatley M, Bhargava R, Hoskinson M, Hao C and Colmers W. Pediatric temporal lobectomy for epilepsy. Pediatr Neurosurg 2003; 38(4):195-205.

Song JH, Song DK, Pyrzynska P, Petruk KC, Van Meir EG and Hao C. TRAIL induces apoptosis in human glioma cells through extrinsic and intrinsic pathways. Brain Pathol 2003; 13 (4): 539 -553.

Sinclair DB, Aronyk KE, Synder TJ, Wheatley BM, McKean JD, Bhargava R, Hoskinson M, Hao C, Commers WF, Berg M and Mak W. Pediatric epilepsy surgery at the University of Alberta: 1988-2000. Pediatr Neurol 2003;29(4):302-311.

Song JH, Song DK, Herlyn M, Petruk KC and Hao C. Cisplatin down-regulation of cellular Fas-associated death domain-like interleukin-1b-converting enzyme-like inhibitory proteins to restore tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in human melanoma cells. Clin Cancer Res 2003; 9 (11): 4255-4266.

Hao C, Parney IF, Roa WH, Turner J, Petruk KC and Ramsay DA. Cytokine and cytokine receptor mRNA expression in human glioblastomas: evidence of Th1, Th2 and Th3 cytokine dysregulation. Acta Neuropathol (Berl). 2002; 103(2):171-178.

Xiao C, Yang BF, Asadi N, Beguinot F and Hao C. TRAIL-induced DISC and its modulation by c-FLIP and PED/PEA-15 in glioma cells. J Biol Chem 2002; 277(28):25020-25025.

Zhou Y, Larsen PH, Hao C and Yong VW. CXCR4 is a major chemokine receptor on glioma cells and mediates their survival. J Biol Chem 2002; 277 (51): 49481-49487

Wang CX, Reece C, Wrathall JR, Shuaib A, Olschowka JA and Hao C. Expression of tumor necrosis factor alpha and its mRNA in the spinal cord following a weight-drop injury. NeuroReport 2002; 13(11): 1391-1393.

Hao C, Beguinot F, Condorelli G, Trencia A, Van Meir EG, Yong WV, Parney IF, Roa WH and Petruk KC. Induction and Intracellular Regulation of TRAIL Mediated Apoptosis in Human Malignant Glioma Cells. Cancer Res 2001; 61(3):1162-1170.

Catania A, Urban S, Yan E, Hao C, Barron G and Allalunis-Turner J. Expression and localization of cyclin dependent kinase 5 in apoptotic human glioma cells. Neuro-Oncol 2001; 3(2):89-98.

Mercer DF, Schiller DE, Elliott JF, Douglas DN, Hao C, Rinfret A, Addison B, Fischer KP, Churchill, TA, Tyrrell LJ and Kneteman NM. Hepatitis C virus replication in mice with chimeric human livers. Nature Med 2001; 7(8):927-933.

Sinclair DB, Wheatley M, Aronyk K, Hao C, Snyner T, Javidan M and McKean JDS. Pathology and neuroimaging in pediatric temporal lobectomy for intractable epilepsy. Pediatr Neurosurg 2001; 35(5):239-246.

Jennings LL, Hao C, Cabrita MA, Vickers MF, Baldwin SA, Young JD and Cass CE. Distinct regional distribution of human equilibrative nucleoside transporter proteins 1 and 2 (hENT1 and hENT2) in the central nervous system. Neuropharmacol 2001; 40(5):722-731.

Parney IF, Hao C, and Petruk KC. Glioma immunology and immunotherapy. Neurosurgery 2000; 46(4):778-791.

Byers DM, Rose SD, Cook HW, Hao C and Fedoroff S. Lipopolysaccharide induction of MARCKS-related protein and cytokine secretion are differentially impaired in microglia from LPS-nonresponsive (C3H/HeJ) mice. Neurochem Res. 1998; 23(12): 1493-1499.

Mackenzie IRA, Hao C and Munoz DG. The role of microglia in senile plaque formation. Neurobiol Ageing. 1995; 16(5): 797-804.

Richardson A, Hao C and Fedoroff S.Microglia progenitor cells: A subpopulation in cultures of mouse neopallial astroglia. Glia. 1993; 7(1):25-33.

Fedoroff S and Hao C. Origin of microglia and their regulation by astroglia. Adv Exp Med Biol. 1991; 296:135-142.

Hao C, Richardson A and Fedoroff S. Macrophage-like cells originate from neuroepithelium in culture: Characterization and properties of the macrophage-like cells. Int J Dev Neurosci. 1991; 9(1):1-14.

Hao C, Guilbert LJ and Fedoroff S. Production of colony stimulating factor-1 (CSF-1) by mouse astroglia in vitro. J Neurosci Res. 1990; 27(3):314-323.

Book Chapters -

Bellail A, Mulligan P, Hao C. Chapter 41. Targeting TRAIL apoptotic pathways for glioblastoma therapy. In: CNS Cancer, Cancer Drug Discovery and Development. Ed: Van Meir EG. Humana Press (Springer), 2009; pp 977-1009.

Van Meir EG, Hao C, Post D, Liau LM, and Brat DJ. Chapter 18. Therapeutic targeting of the molecular pathways that induce brain tumor development. In: Genomic and Molecular Neuro-Oncology. Eds: Wei Zhang and Gregory N. Fuller. Jones and Bartlett Publishers, Inc., 2004; pp 303 - 331.

Hao C, Song JH, Vilimanovich U, Kneteman NM. Chapter 6. Modulation of TRAIL Signaling Complex. In: Vitamins and Hormones. Ed: Gerry Litwack, Academic Press (Elsevier), 2004, 67:81-99.

Fedoroff S, Hao C, Ahmed I and Guilbert LJ. Paracrine and autocrine signalling in regulation of microglia survival. In: Biology and Pathology of Astrocyte-Neuron Interactions. Eds: S Fedoroff, BHJ Juurlink & R Doucette. Plenum Press, New York. 1993; pp 247-261.

Hao C, Richardson A. and Fedoroff S. Chapter 7. Isolation of microglia from mouse astroglia cultures. In: Protocols for Neural Cell Culture. Eds: Fedoroff S and Richardson A. Humana Press, Totowa, New Jersey, 1992; pp 97-104.