Winship Cancer Institute
1365-C Clifton Road NE Room 5082
Atlanta, GA 30322
Member, Winship Cancer Institute, Emory University School of Medicine
Attending Pathologist (Neuropathology), Emory University Hospital
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
- apoptotic pathways and therapeutic targets in cancers and cancer stem cells
The goal of my research is to illustrate apoptotic pathways in glioblastoma, the most malignant brain tumor, for the development of cancer therapeutic agents targeting the apoptotic pathways. There are two major projects currently going on in my research lab. A. The objective of the first project is to molecularly dissect TRAIL-induced apoptotic pathway and its targeted cancer therapies. 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. To explore the molecular mechanism in TRAIL resistance, we have identified the receptor-associated proteins complex. 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. Our current efforts therefore focus on (i) the characterization of the E3 ligases-mediated ubiquitination of the substrate proteins in the complex, (ii) the investigation of how the ubiquitin 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 process, and (iv) the identification of the E3 ligases and/or their substrate proteins as biomarkers predicting the cancer responsiveness to TRAIL-based therapies. This project is currently funded by NIH R01. B. The objective of the second project is to establish glioblastoma-derived cancer stem cells as cancer therapeutic targets. One of the major obstacles in glioblastoma research and drug discovery is the lack of suitable research models for studying cancer signaling pathways and screening pathways-targeted therapies. In collaboration with Dr Jeffrey Olson, neurosurgery, we have established glioblastoma-derived cancer stem cells. In this project, we will analyze the stem cells first to determine whether they retain the genomic properties of the original tumors and can be therefore used as the tumor models. We will further determine whether apoptotic pathways exist in the stem cells and if so, can be therapeutically targeted. Finally, we will examine receptors-tyrosine kinase-induced cell growth pathways in the stem cells and thus determine whether targeting of which of the receptors can inhibit the stem cell renewal and progress. At the completion of this project, we hope to identify cancer therapeutics that can target the cancer stem cells.
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
1997 FRCPC Fellow of Royal College of Physicians & Surgeons of Canada
1997 Certificate in Neuropathology Royal College of Physicians and Surgeons of Canada
Bellail A, Olson JJ, Yang X, Chen Z, Hao C. A20 ubiquitin ligase-mediated polyubiquitination of RIP1 inhibits caspase-8 cleavage and TRAIL-induced apoptosis in glioblastoma. Cancer Discovery Feb 17, 2012; 2(2); 140-155 (Jan 24, OnlineFirst, AACR press release).
Bellail AC, Hao C. The roadmap of clinical trials of TRAIL agonists for cancer therapies: what is next (Editorial)? Expert Rev. Anticancer Ther 2012 May, 12(5):547-9.
Zheng Z, Ng WL, Zhang X, Olson JJ, Hao C, Curran WJ, Wang Y. RNAI-mediated targeting of non-coding and coding sequences in DNA repair gene messages efficiently radiosensitizes human tumor cells. Cancer Res 2012 Jan 11 [Epub ahead of print].
Li B, Gao S, Wei F, Bellail AC, Hao C, Liu T. Simultaneous targeting of EGFR and mTOR inhibits the growth of colorectal carcinoma cells. Oncol Rep 2012 Jul 28 (1):15-20. Doi: 10.3892 or 2012.1786. Epub ahead of print.
Bellail AC, Hao C. TRAIL apoptotic pathway-targeted therapies for NSCLC (Highlight). Translational Lung Cancer Research Mar 4, 2012. DOI:10.3978/j.issn. 2218-6751.2012.02.02.
Dong B, Lv G, Wang Q, Wei F, Bellail AC, Hao C, Wang G. Targeting A20 enhances TRAIL-induced apoptosis in hepatocellular carcinoma cells. Biochem Biophys Res Commun 2012 Feb 10;418(2):433-8. Epub 2012 Jan 20.
Wei F, Liu Y, Bellail AC, Olson JJ, Sun S-Y, Guoyue Lu, Lijuan Ding, Changji Yuan, Wang G, Hao C. K-Ras mutation-mediated IGF-1-induced feedback ERK activation contributes to the rapalog resistance in pancreatic ductal adenocarcinomas. Cancer Lett 2012 (Feb 14, 2012 online).
Lu J, McEachern D, Sun H, Bai L, Peng Y, Qiu S, Miller RS, Liao J, Yi H, Liu M, Bellail A, Hao C, Sun SY, Ting AT, Wang S. Therapeutic potential and molecular mechanism of a novel, potent, nonpeptide, Smac mimetic SM-164 in combination with TRAIL for cancer treatment. Mol Cancer Ther 2011 May; 10(5):902-14. Epub2011 Mar 3.
Chan CB, Liu X, Pradoldej S, Hao C, An J, Yepes M, Luo HR, Ye K. Phosphoinositide 3-kinase enhancer regulates neuronal dendritogenesis and survival in neocortex. J Neurosci 2011 June 1; 31(22): 8083-92. Epub 2011 Aug 25.
Qi L, Bellail AC, Rossi MR, Zhang Z, Peng H, Hunter S, Cohen C, Moreno CS, Olson JJ, Li S, Hao C. Heterogeneity of primary glioblastoma cells in the expression of caspase-8 and the response to TRAIL-induced apoptosis. Apoptosis 2011 Nv; 16(11):1150-64 [Epub 2011 Aug 30].
Chen S, Cao W, Yue P, Hao C, Khuri FR, Sun S-Y. Celecoxib promotes c-FLIP degradation through Akt-independent inhibition of GSK3. Cancer Res 2011 Oct 1;71(19):6270-81 Epub 2011 Aug 25.
Ding L, Yuan C, Wei F, Wang G, Zhang J, Bellail A, Zhang Z, Olson JJ. Hao C. Cisplatin restores TRAIL apoptotic pathway in glioblastoma-derived stem cells through up-regulation of DR5 and down-regulation of c-FLIP. Cancer Invest 2011 Oct; 29(8):511-20. Epub 2011 Aug 30.
Jiang Y, Ma Z, Xin G, Yan H, Xu H, Hao C, Niu J and Li W. Th1 and Th2 Immune Response in Chronic Hepatitis B Patients during a Long-Term Treatment with Adefovir Dipivoxil. Mediators Inflamm 2010;2010:143026. Epub 2010 Nov 29.
Lu GU, Liu YH, Wei F, Ji B, Hao C, Wang GY. Synergistic effect of celecoxib on tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in hepatocellular carcinoma cells. Cancer Invest 2010 Jul; 28(6):629-634.
Hadjipanayis CG, Schuette AJ, Boulis N, Hao C, Barrow DL, Teo C. Full scope of options. Neurosurgery. 2010 Jul;67(1):197-203
Yan D, Ng WL, Zhang X, Wang P, Zhang Z, Mo Y-Y, Mao H, Hao C, Olson J, Curran W, Wang Y. Targeting DNA-PKcs and ATM with miR-101 Sensitizes Tumors to Radiation. Plos One 2010 July 1; 5(7):e11397.
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 2010 June; 14(6a):1303-1317 [Published Online: May 11, 2009]
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.
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.
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.
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.
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
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.
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.
Parney IF, Chang LJ, Farr-Jones MA, Hao C, Smylie M, Petruk KC. Technical hurdles in a pilot clinical trial of combined B7-2 and GM-CSF immunogene therapy for glioblastomas and melanomas. J Neurooncol 2006 May; 78(1):71-80.
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
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
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
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Findlay JM, Hao C, Emery D. Nonatherosclerotic fusiform cerebral aneurysms. Can J Neurol Sci 2002 Feb; 29(1): 41-48.
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.
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.
Koski S, Hao C, Mackey JR, Fields ALA. Wernicke encephalopathy in association with malignancy: A case Report and Review of the Literature. Curr Oncol 2001; 8 (2):104-108.
Maeda T, Hao C, Tron VA. UV induced regulation of TNF receptor superfamily decoy receptors in human keratinocytes. J Cutan Med Surg 2001 Jul-Aug; 5(4):294-298.
Yee D, Hao C, Chen H, Fulton D, Petruk KC, Roa WH. Effect of radiation on cytokine and cytokine receptor messenger-RNA profiles in p53 wild and mutated human glioblastoma cell lines. Clin Invest Med 2001 Apr; 24(2):76-82
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.
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.
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.
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.