Faculty

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Joseph G Hacia, PhD
Associate Professor of Biochemistry & Molecular Biology
Vice Chair For Medical Education
Biochemistry and Molecular Biology
CSC 261 2250 Alcazar Street Health Sciences Campus Los Angeles
+1 323 442 3030

Overview

Joe Hacia, an Associate Professor of Biochemistry and Molecular Biology, is a medical geneticist who obtained his undergraduate training at Rutgers University and graduate training at the California Institute of Technology. Prior to joining the USC faculty, he obtained his post-doctoral training at the National Human Genome Research Institute (NHGRI) of the National Institutes of Health (NIH).

The Hacia laboratory focuses on developing therapies for genetic disorders caused by impaired peroxisome assembly, structure, and function. His group focuses on peroxisome biogenesis disorders (PBDs), which include Zellweger spectrum disorder (PBD-ZSD) and rhizomelic chondrodysplasia punctata (RCDP). Affected children frequently show progressive loss of vision and hearing, brain and liver dysfunction, craniofacial dysmorphism, and enamel defects. They also have interest in therapeutic development for the related peroxisomal disorder X-linked adrenoleukodystrophy (X-ALD), including the childhood cerebral ALD (CCALD) form of disease that results in inflammatory demyelination and adult onset adrenomyeloneuropathy (AMN) that affects spinal cord function and leads to loss of lower limb functions.

The Hacia laboratory is involved in high-content screening of large chemical libraries as well as retinal gene therapy and cell transplantation therapy projects. As part of these efforts, they developed patient-specific induced pluripotent stem cells (iPSCs) as cell culture models of peroxisomal disorders. By working closely with the physician-scientists and patient advocacy groups, the Global Foundation for Peroxisomal Disorders (GFPD) (http://www.thegfpd.org/) and RhizoKids International (http://www.rhizokids.com/), they seek to translate their research into improved treatments in the near future.

The Hacia laboratory has also used comparative genomics and lipidomics approaches to uncover evidence that peroxisomal metabolism has been strongly influenced by primate diets. They wish to use the knowledge gained from these projects to benefit the health of captive non-human primates and people with peroxisomal disorders.

Research Interests: medical genetics, molecular therapeutics
Diseases Models: cultured fibroblasts, induced pluripotent stem cells, genetically engineered mice
Consortia: Global Foundation for Peroxisomal Disorders and RhizoKids International

Awards

Howard Hughes Medical Institute Predoctoral Fellow

American Society of Human Genetics (ASHG) Postdoctoral Translational Research Award

V Foundation Scholar

Editorial Board of Genome Research

Member of NIH Comparative Genomics Study Section

Editorial Board Nucleic Acids Research

Chaired Session at ASHG on Early Diagnosis and Treatment of CNS-based Metabolic Disorders

Editorial Board BMC Genomics

Year 1 USC Medical Teaching Award

Chaired Session at ASHG on Targeted Drug Therapies for Progressive Genetic Disorders

Year 2 USC Medical Teaching Award

Editorial Board BMC Medical Genomics

Chaired Session at ASHG meeting on Targeted Drug Therapies for Progressive Genetic Disorders

Member, Scientific Advisory Board of the Global Foundation for Peroxisomal Disorders

External Reviewer, Institute of Medicine Review of California Institute for Regenerative Medicine

Chaired Session at ASHG meeting on Early Diagnosis and Treatment of CNS-based Metabolic Disorders

Member of Chemical Gene & Cell Therapy Committee of the American Society of Gene & Cell Therapy

Member of X-linked Adrenoleukodystrophy (ALD) Connect Workgroup on Therapy Review

Year 1 USC Medical Teaching Award

Year 1 Outstanding Course Award for USC Medical Teaching

Publications

Shahabi A, Lewinger JP, Ren J, April C, Sherrod AE, Hacia JG, Daneshmand S, Gill I, Pinski JK, Fan JB, Stern MC. Novel Gene Expression Signature Predictive of Clinical Recurrence After Radical Prostatectomy in Early Stage Prostate Cancer Patients. Prostate. 2016 Oct; 76(14):1239-56. View in: PubMed

Braverman NE, Raymond GV, Rizzo WB, Moser AB, Wilkinson ME, Stone EM, Steinberg SJ, Wangler MF, Rush ET, Hacia JG, Bose M. Peroxisome biogenesis disorders in the Zellweger spectrum: An overview of current diagnosis, clinical manifestations, and treatment guidelines. Mol Genet Metab. 2016 Mar; 117(3):313-21. View in: PubMed

Wang XM, Yik WY, Zhang P, Lu W, Huang N, Kim BR, Shibata D, Zitting M, Chow RH, Moser AB, Steinberg SJ, Hacia JG. Induced pluripotent stem cell models of Zellweger spectrum disorder show impaired peroxisome assembly and cell type-specific lipid abnormalities. Stem Cell Res Ther. 2015; 6(1):158. View in: PubMed

Ramaswamy K, Yik WY, Wang XM, Oliphant EN, Lu W, Shibata D, Ryder OA, Hacia JG. Derivation of induced pluripotent stem cells from orangutan skin fibroblasts. BMC Res Notes. 2015; 8(1):577. View in: PubMed

Hiebler S, Masuda T, Hacia JG, Moser AB, Faust PL, Liu A, Chowdhury N, Huang N, Lauer A, Bennett J, Watkins PA, Zack DJ, Braverman NE, Raymond GV, Steinberg SJ. The Pex1-G844D mouse: A model for mild human Zellweger spectrum disorder. Mol Genet Metab. 2014 Apr; 111(4):522-32. View in: PubMed

Yin K, Hacia JG, Zhong Z, Paine ML. Genome-wide analysis of miRNA and mRNA transcriptomes during amelogenesis. BMC Genomics. 2014; 15(1):998. View in: PubMed

Pelikan RC, Iwata J, Suzuki A, Chai Y, Hacia JG. Identification of candidate downstream targets of TGFß signaling during palate development by genome-wide transcript profiling. J Cell Biochem. 2013 Apr; 114(4):796-807. View in: PubMed

Moser AB, Hey J, Dranchak PK, Karaman MW, Zhao J, Cox LA, Ryder OA, Hacia JG. Diverse captive non-human primates with phytanic acid-deficient diets rich in plant products have substantial phytanic acid levels in their red blood cells. Lipids Health Dis. 2013; 12:10. View in: PubMed

Lacruz RS, Hacia JG, Bromage TG, Boyde A, Lei Y, Xu Y, Miller JD, Paine ML, Snead ML. The circadian clock modulates enamel development. J Biol Rhythms. 2012 Jun; 27(3):237-45. View in: PubMed

Lacruz RS, Smith CE, Bringas P, Chen YB, Smith SM, Snead ML, Kurtz I, Hacia JG, Hubbard MJ, Paine ML. Identification of novel candidate genes involved in mineralization of dental enamel by genome-wide transcript profiling. J Cell Physiol. 2012 May; 227(5):2264-75. View in: PubMed

Han D, Zhao H, Parada C, Hacia JG, Bringas P, Chai Y. A TGFß-Smad4-Fgf6 signaling cascade controls myogenic differentiation and myoblast fusion during tongue development. Development. 2012 May; 139(9):1640-50. View in: PubMed

Iwata J, Hacia JG, Suzuki A, Sanchez-Lara PA, Urata M, Chai Y. Modulation of noncanonical TGF-ß signaling prevents cleft palate in Tgfbr2 mutant mice. J Clin Invest. 2012 Mar 1; 122(3):873-85. View in: PubMed

Iwata J, Tung L, Urata M, Hacia JG, Pelikan R, Suzuki A, Ramenzoni L, Chaudhry O, Parada C, Sanchez-Lara PA, Chai Y. Fibroblast Growth Factor 9 (FGF9)-Pituitary Homeobox 2 (PITX2) Pathway Mediates Transforming Growth Factor ß (TGFß) Signaling to Regulate Cell Proliferation in Palatal Mesenchyme during Mouse Palatogenesis. J Biol Chem. 2012 Jan 20; 287(4):2353-63. View in: PubMed

Wang XM, Yik WY, Zhang P, Lu W, Dranchak PK, Shibata D, Steinberg SJ, Hacia JG. The gene expression profiles of induced pluripotent stem cells from individuals with childhood cerebral adrenoleukodystrophy are consistent with proposed mechanisms of pathogenesis. Stem Cell Res Ther. 2012; 3(5):39. View in: PubMed

Levesque S, Morin C, Guay SP, Villeneuve J, Marquis P, Yik WY, Jiralerspong S, Bouchard L, Steinberg S, Hacia JG, Dewar K, Braverman NE. A founder mutation in the PEX6 gene is responsible for increased incidence of Zellweger syndrome in a French Canadian population. BMC Med Genet. 2012; 13:72. View in: PubMed

Lacruz RS, Smith CE, Chen YB, Hubbard MJ, Hacia JG, Paine ML. Gene-expression analysis of early- and late-maturation-stage rat enamel organ. Eur J Oral Sci. 2011 Dec; 119 Suppl 1:149-57. View in: PubMed

Dranchak PK, Di Pietro E, Snowden A, Oesch N, Braverman NE, Steinberg SJ, Hacia JG. Nonsense suppressor therapies rescue peroxisome lipid metabolism and assembly in cells from patients with specific PEX gene mutations. J Cell Biochem. 2011 May; 112(5):1250-8. View in: PubMed

Moser AB, Steinberg SJ, Watkins PA, Moser HW, Ramaswamy K, Siegmund KD, Lee DR, Ely JJ, Ryder OA, Hacia JG. Human and great ape red blood cells differ in plasmalogen levels and composition. Lipids Health Dis. 2011; 10:101. View in: PubMed

Lacruz RS, Lakshminarayanan R, Bromley KM, Hacia JG, Bromage TG, Snead ML, Moradian-Oldak J, Paine ML. Structural analysis of a repetitive protein sequence motif in strepsirrhine primate amelogenin. PLoS One. 2011; 6(3):e18028. View in: PubMed

Wang XM, Greiner TC, Bibikova M, Pike BL, Siegmund KD, Sinha UK, Müschen M, Jaeger EB, Weisenburger DD, Chan WC, Shibata D, Fan JB, Hacia JG. Identification and functional relevance of de novo DNA methylation in cancerous B-cell populations. J Cell Biochem. 2010 Mar 1; 109(4):818-27. View in: PubMed

Watkins PA, Moser AB, Toomer CB, Steinberg SJ, Moser HW, Karaman MW, Ramaswamy K, Siegmund KD, Lee DR, Ely JJ, Ryder OA, Hacia JG. Identification of differences in human and great ape phytanic acid metabolism that could influence gene expression profiles and physiological functions. BMC Physiol. 2010; 10:19. View in: PubMed

Yik WY, Steinberg SJ, Moser AB, Moser HW, Hacia JG. Identification of novel mutations and sequence variation in the Zellweger syndrome spectrum of peroxisome biogenesis disorders. Hum Mutat. 2009 Mar; 30(3):E467-80. View in: PubMed

Toleno DM, Renaud G, Wolfsberg TG, Islam M, Wildman DE, Siegmund KD, Hacia JG. Development and evaluation of new mask protocols for gene expression profiling in humans and chimpanzees. BMC Bioinformatics. 2009; 10:77. View in: PubMed

Magda D, Lecane P, Wang Z, Hu W, Thiemann P, Ma X, Dranchak PK, Wang X, Lynch V, Wei W, Csokai V, Hacia JG, Sessler JL. Synthesis and anticancer properties of water-soluble zinc ionophores. Cancer Res. 2008 Jul 1; 68(13):5318-25. View in: PubMed

Hacia JG, Lee CC, Jimenez DF, Karaman MW, Ho VV, Siegmund KD, Tarantal AF. Age-related gene expression profiles of rhesus monkey bone marrow-derived mesenchymal stem cells. J Cell Biochem. 2008 Mar 1; 103(4):1198-210. View in: PubMed

Magda D, Lecane P, Prescott J, Thiemann P, Ma X, Dranchak PK, Toleno DM, Ramaswamy K, Siegmund KD, Hacia JG. mtDNA depletion confers specific gene expression profiles in human cells grown in culture and in xenograft. BMC Genomics. 2008; 9:521. View in: PubMed

Ku TK, Nguyen DC, Karaman M, Gill P, Hacia JG, Crowe DL. Loss of p53 expression correlates with metastatic phenotype and transcriptional profile in a new mouse model of head and neck cancer. Mol Cancer Res. 2007 Apr; 5(4):351-62. View in: PubMed

Wang Z, Lecane PS, Thiemann P, Fan Q, Cortez C, Ma X, Tonev D, Miles D, Naumovski L, Miller RA, Magda D, Cho DG, Sessler JL, Pike BL, Yeligar SM, Karaman MW, Hacia JG. Synthesis and biologic properties of hydrophilic sapphyrins, a new class of tumor-selective inhibitors of gene expression. Mol Cancer. 2007; 6:9. View in: PubMed

Pike BL, Groshen S, Hsu YH, Shai RM, Wang X, Holtan N, Futscher BW, Hacia JG. Comparisons of PCR-based genome amplification systems using CpG island microarrays. Hum Mutat. 2006 Jun; 27(6):589-96. View in: PubMed

Greiner TC, Dasgupta C, Ho VV, Weisenburger DD, Smith LM, Lynch JC, Vose JM, Fu K, Armitage JO, Braziel RM, Campo E, Delabie J, Gascoyne RD, Jaffe ES, Muller-Hermelink HK, Ott G, Rosenwald A, Staudt LM, Im MY, Karaman MW, Pike BL, Chan WC, Hacia JG. Mutation and genomic deletion status of ataxia telangiectasia mutated (ATM) and p53 confer specific gene expression profiles in mantle cell lymphoma. Proc Natl Acad Sci U S A. 2006 Feb 14; 103(7):2352-7. View in: PubMed

Lecane PS, Karaman MW, Sirisawad M, Naumovski L, Miller RA, Hacia JG, Magda D. Motexafin gadolinium and zinc induce oxidative stress responses and apoptosis in B-cell lymphoma lines. Cancer Res. 2005 Dec 15; 65(24):11676-88. View in: PubMed

Magda D, Lecane P, Miller RA, Lepp C, Miles D, Mesfin M, Biaglow JE, Ho VV, Chawannakul D, Nagpal S, Karaman MW, Hacia JG. Motexafin gadolinium disrupts zinc metabolism in human cancer cell lines. Cancer Res. 2005 May 1; 65(9):3837-45. View in: PubMed

Karaman MW, Groshen S, Lee CC, Pike BL, Hacia JG. Comparisons of substitution, insertion and deletion probes for resequencing and mutational analysis using oligonucleotide microarrays. Nucleic Acids Res. 2005; 33(3):e33. View in: PubMed

Smith E, Meyerrose TE, Kohler T, Namdar-Attar M, Bab N, Lahat O, Noh T, Li J, Karaman MW, Hacia JG, Chen TT, Nolta JA, Müller R, Bab I, Frenkel B. Leaky ribosomal scanning in mammalian genomes: significance of histone H4 alternative translation in vivo. Nucleic Acids Res. 2005; 33(4):1298-308. View in: PubMed

Leclerc N, Luppen CA, Ho VV, Nagpal S, Hacia JG, Smith E, Frenkel B. Gene expression profiling of glucocorticoid-inhibited osteoblasts. J Mol Endocrinol. 2004 Aug; 33(1):175-93. View in: PubMed

Lipkin SM, Rozek LS, Rennert G, Yang W, Chen PC, Hacia J, Hunt N, Shin B, Fodor S, Kokoris M, Greenson JK, Fearon E, Lynch H, Collins F, Gruber SB. The MLH1 D132H variant is associated with susceptibility to sporadic colorectal cancer. Nat Genet. 2004 Jul; 36(7):694-9. View in: PubMed

Nagpal S, Karaman MW, Timmerman MM, Ho VV, Pike BL, Hacia JG. Improving the sensitivity and specificity of gene expression analysis in highly related organisms through the use of electronic masks. Nucleic Acids Res. 2004; 32(5):e51. View in: PubMed

Karaman MW, Houck ML, Chemnick LG, Nagpal S, Chawannakul D, Sudano D, Pike BL, Ho VV, Ryder OA, Hacia JG. Comparative analysis of gene-expression patterns in human and African great ape cultured fibroblasts. Genome Res. 2003 Jul; 13(7):1619-30. View in: PubMed

Fang NY, Greiner TC, Weisenburger DD, Chan WC, Vose JM, Smith LM, Armitage JO, Mayer RA, Pike BL, Collins FS, Hacia JG. Oligonucleotide microarrays demonstrate the highest frequency of ATM mutations in the mantle cell subtype of lymphoma. Proc Natl Acad Sci U S A. 2003 Apr 29; 100(9):5372-7. View in: PubMed

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