Zihua Hu, PhD

Bioinformatics and computational biology support include the development of customized tools and approaches to support faculty led research and advanced data analysis and mining for research projects and funding application, those include:

• Gene regulation: including functional promoter, transcriptional regulatory network, and miRNA analyses.
• RNA-Seq, Chip-seq, Chip-RNA, ChiP-chip, Affymetrix GeneChip, and cDNA microRNA data analyses.
• Genome scale sequence analysis: ESTs, genomes, etc.
• Biological data analysis and mining using statistical approaches.
• Pathway analyses, Protein and metabolic profiling.
• Development of bioinformatics tools for the above analyses.

I am currently pursuing a variety of computational and genomics topics and collaborating with colleagues on large-scale genomics projects, including developing statistical and computational approaches for gene expression, transcriptional regulatory network, and large-scale sequence analyses. My independent research interest is on the global gene regulation at both transcriptional and post-transcriptional levels. The major focus is to use computational approaches to integrate high-throughput biological data to ask questions and understand gene regulation mechanisms in a systems level. These include:

Transcriptional Regulation of Gene expression. Regulation of gene expression plays a key role in many cellular processes, including proliferation, senescence and development. Transcription is a major target for regulation of gene expression in all organisms, and failure to correctly regulate transcription is a cause of many diseases, notably cancer. Indeed, many human oncogenes are themselves transcriptional regulators. Transcriptional regulation also plays a key role in the virulence of many human pathogens. Therefore it is vital to understand the mechanisms by which transcription is regulated. My research is focused on the mechanisms of transcriptional regulation of disease-related gene expression;My research also includes conducting genome-wide studies of regulatory elements to elucidate the regulatory logic of transcription factors and their corresponding binding sites in controlling gene expression and applying the developed statistical and computational approaches from the above research to collaborative projects.

Post-transcriptional Gene Regulation by microRNAs. microRNAs will shape biology and change the traditional concepts of the molecular biology. My research focus is to uncover the widespread influence of miRNAs on disease-related gene expression.

Genetic Variation and Diseases.  Genetic variations play important roles in the regulation of gene expression such as miRNA and SNPs.  We are interested in addressing the questions as how different miRNAs and SNPs might contribute separately or synergistically to specific phenotypes such as diseases.

1.     Hu Z, Jiang K, Frank MB, Chen Y, Jarvis JN (2016) Complexity and Specificity of the Neutrophil Transcriptomes in Juvenile Idiopathic Arthritis. Sci Rep. 6:27453. doi: 10.1038/srep27453

2.     Jiang H, Xu Z, Zhong P, Ren Y, Liang G, Schilling HA, Hu Z, Zhang Y, Wang X, Chen S, Yan Z, and Feng J (2015) Cell cycle and p53 gate the direct conversion of human fibroblasts to dopaminergic neurons. Nature Communication. Dec 7;6:10100. doi: 10.1038/ncomms10100

3.     Sapkota D, Chintala H, Wu F, Fliesler SJ, Hu Z, Mu X (2014) Onecut1 and Onecut2 redundantly regulate multiple retinal cell fates during development. PNAS.111(39):E4086-95.

4.     Li R, Wu F, Ruonala R, Sapkota D, Hu Z, Mu X (2014) Isl1 and Pou4f2 form a complex to regulate target genes in developing retinal ganglion cells. PLoS One.18;9(3):e92105.

5.     Kuo SM, Chan WC, Hu Z (2014) Wild-type and IL10-null mice have differential colonic epithelial gene expression responses to dietary supplementation with synbiotic Bifidobacterium animalis subspecies lactis and inulin. J Nutr.144 (3):245-51.

6.     Jiang K, Hu Z, Chen Y, Jarvis JN (2014) A176: deep sequencing reveals differential small RNA expression in serum exosomes of children with juvenile idiopathic arthritis. Arthritis Rheumatol. 66 Suppl 11:S230.

7.     Li XM, Yan QY, Xie SQ, Hu W, Yu YH, Hu Z* (2013) Gut Microbiota Contributes to the Growth of Fast-growing Transgenic Common Carp (Cyprinus carpio L.). PLoS One. 8(5): e64577.

8.     Patel M, Hu Z, Bard J, Jamison J, Cai Q, Hu BH (2013) Transcriptome Characterization by RNA-Seq Reveals the Involvement of the Complement Components in Noise-Traumatized Rat Cochleae. Neuroscience. May 29.

9.     Patel M, Cai Q, Ding D, Salvi R, Hu Z, Hu BH (2013) The miR-183/Taok1 Target Pair Is Implicated in Cochlear Responses to Acoustic Trauma. PLoS One. 8(3):e58471

10.  Pan YZ, Zhou A, Hu Z, Yu AM (2013) Small Nucleolar RNA-Derived Microrna hsa-Mir-1291 Modulates Cellular Drug Disposition Through Direct Targeting of ABC Transporter ABCC1. Drug Metab Dispos. May 16

11.  Bruno AE, Li L, Kalabus JL, Pan Y, Yu A, Hu Z* (2012) miRdSNP: a database of disease-associated SNPs and microRNA target sites on 3'UTRs of human genes. BMC Genomics. 13:44.

12.  Kuo SM, Burl LR, Hu Z (2012) Cellular phenotype-dependent and -independent effects of vitamin C on the renewal and gene expression of mouse embryonic fibroblasts. PLoS One. 7:e32957

13.  Hu BH, Cai Q, Hu Z, Patel M, Bard J, Jamison J, Coling D (2012) “Metalloproteinases and their associated genes contribute to the functional integrity and noise-induced damage in the cochlear sensory epithelium”. J Neurosci.32:14927-41.

14.  Shu W, Lin Y, Hua R, Luo Y, He N, Fang L, Tan J, Lu J, Hu Z, Yuan Z (2012) Cutaneomucosal venous malformations are linked to the TIE2 mutation in a large Chinese family. Exp Dermatol. 21:456-7.

15.  Milliman EJ, Hu Z, Yu MC (2012) Genomic insights of protein arginine methyltransferase Hmt1 binding reveals novel regulatory functions. BMC Genomics. 13(1):728

16.  Hu Z*, Bruno A (2011) The influence of 3’UTRs on microRNA function inferred from human SNP data. Comparative and Functional Genomics.

17.  Li X, Pan YZ, Seigel GM, Hu Z, Huang M, Yu AM (2011)  Breast cancer resistance protein BCRP/ABCG2 regulatory microRNAs (hsa-miR-328, -519c and -520h) and their differential expression in stem-like ABCG2+ cancer cells. Biochem Pharmacol. 15;81(6):783-92.

18.  Hu Z*, Gallo S (2010) Identification of interacting transcription factors controlling gene expression in human tissues. BMC Genomics;11:49.

19.  Hu Z*, Gulec S, Collins JF (2010) Cross-Species Comparison of Genome-Wide Gene Expression Profiles Reveals a Preferential Induction of Hypoxia Inducible Factor Responsive Genes in Iron Deprived Intestinal Epithelial Cells. Am J Physiol Cell Physiol. 299(5):C930-8.

20.  Aalinkeel R, Hu Z, Nair BB, Sykes DE, Reynolds JL, Mahajan SD, Schwartz SA (2010) Genomic analysis highlights the role of the JAK-STAT signaling in the anti-proliferative effects of dietary flavonoid—Ashwagandha’in prostate cancer cells Evidence-Based Complementary and Alternative Medicine 7 (2), 177-187

21.  Hu Z* (2009) Insight into microRNA regulation by analyzing the characteristics of their targets in humans. BMC Genomics;10:594.

22.  Mahajan SD, Aalinkeel R, Reynolds JL, Nair BB, Sykes DE, Hu Z, Bonoiu A, Ding H, Prasad PN, Schwartz SA (2009) Therapeutic targeting of DARPP-32: a key signaling molecule in the dopiminergic pathway for the treatment of opiate addiction. Int Rev Neurobiol. 88:199-222.

23.  Lindemann MJ, Hu Z, M Benczik, KD Liu, SL Gaffen (2008) Differential Regulation of the IL-17 Receptor by yc Cytokines: Inhibitory Signaling by the PI 3-kinase Pathway. J Biol Chem;283(20):14100-14108.

24.  Ananthi J. Asirvatham, Christopher J. Gregorie, Hu Z, William J. Magner and Thomas B. Tomasi (2008) MicroRNA Targets in Immune Genes and the Dicer/Argonaute and ARE Machinery Components. Molecular Immunology; 45(7):1995-2006.

25.  Ruckdeschel E, Kirkham C, Lesse AJ, Hu Z, Murphy TF (2008) Mining the Moraxella catarrhalis Genome: Identification of Potential Vaccine Antigens Expressed during Human Infection. Infect Immun; 76(4):1599-1607.

26.  James F. Collins, Hu Z, Laura M. Garrick, Michael D. Garrick, Richard W. Browne (2008) Induction of Arachidonate 12-Lipoxygenase in Intestine of Fe-Deficient Rats Results in Production of Biologically Active Lipid Mediators. Am J Physiol Gastrointest Liver Physiol;294(4):G948-962.

27.   Ravikumar A, Hu Z, Balakrishnan B, Donald ES, Reynolds JL, Mahajan SD, Schwartz SA (2008) Genomic Analysis Highlights the Role of the JAK-STAT Signaling in the Anti Proliferative Effects of Dietary Flavonoid- Ashwagandha in Prostate Cancer Cells. eCAM, doi:10.1093/ecam/nem184.

28.   Bindukumar B, SD Mahajan, JL Reynolds, Hu Z, DE Sykes, R Aalinkeel, and SA Schwartz (2008) Genomic and Proteomic Analysis of The Effects of Cannabinoids on Normal Human Astrocytes. Brain Research, 119:1-11.

29.  Hu Z*, Hu B, Collins JF (2007) Prediction of Synergistic Transcription Factors by Function Conservation. Genome Biology, 8:R257.

30.  Hu Z*, Jamie F. Collins (2007) Promoter Analysis of Rat Duodenal Genes Induced During Iron-Deficiency Reveals Enrichment of Conserved SP1 Binding Sites. BMC Genomics, 8:420

31.  Collins JF, Hu Z (2007) Microarray Analysis of Rat Duodenum during Iron- and Copper Deficiency. FASBE21: 934.

32.  Hu Z*, Wilsky GR (2006) Utilization of Two Sample t-test Statistics from Redundant Probe Sets to Evaluate Different Probe Set Algorithms in GeneChip Studies. BMC Bioinformatics, 7:12.

33.  Shen F, Hu Z, Goswami J, Gaffen SL (2006) Identification of Common Transcriptional Regulatory Elements in Interleukin-17 Target Genes. J Biol Chem. 281:24138-24148.

34.   Mahajan SD, Hu Z, Reynolds JL, Aalinkeel R, Schwartz SA, Nair MPN (2006) Methamphetamine Modulates Gene Expression Patterns in Monocyte Derived Mature Dendritic Cells: Implications for HIV-1 Pathogenesis. Mol Diagn Ther. 10:257-269.

35.   Willsky GR, Chi L-H, Liang Y, Gaile DP, Hu Z, Crans DC (2006) Diabetes Altered Gene Expression in Rat Skeletal Muscle Corrected by Oral Administration of Vanadyl Sulfate. Physiological Genomics,26:192-201.

36.  Gallo SM, Li L, Hu Z, Halfon MS (2005) REDfly: A Regulatory Element Database for Drosophila. Bioinformatics, 22:381-383.

37.  Guo M, Rupe M, Danilevskay O, Yang X,  Hu Z (2003) Genome-wide mRNA Profiling Reveals Heterochronic Allelic Variation and a New Imprinted Gene in Hybrid Maize Endosperm. Plant J, 36:30-44.

38.  Hu Z, Poulton JP (1999) Molecular Analysis of (R)-(+)-Mandelonitrile Lyase Microheterogeneity in Black Cherry. Plant Physiology 119: 1535-1546.

39.  Hu Z, Poulton JP (1997) Sequencing, Genomic Organization and Preliminary Promoter Analysis of a Black Cherry (Prunus serotina) (R)-(+)-Mandelonitrile Lyase Gene. Plant Physiology 115: 1359-1369

1. Zihua Hu (2010) "Book review: Sequence Alignment: Methods, Models, Concepts, and Strategies." Am J Hum Biol. May;22(3): 427-428
2. Zihua Hu (2004) "DNA Microarray and Data Analysis". In "Introduction to Bioinformatics", ZhengzhouUniversityPress, pp 153-174.
3. Zihua Hu (2004) "Molecular Databases and Their Applications". In "Introduction to Bioinformatics", ZhengzhouUniversity Press, pp 75-110.
4. Zihua Hu and Ping Liang (2004) "DNA and Protein Sequences Analysis". In "Introduction to Bioinformatics", ZhengzhouUniversityPress, pp 111-135.
5. Zihua Hu and Wei Li (2004) "Elements of Statistics". In "Introduction to Bioinformatics", ZhengzhouUniversity Press, pp 221-261.
6. Browne RW, Garrick MD, Garrick LM, Zihua Hu. Altered Arachidonic Acid Metabolism in the Intestine of Iron and Iron/Copper-Deficient Rats: Strong Induction of Arachidonate 12-Lipoxygenase. Podium Presentation. 2^nd Congress of the International BioIron Society, Kyoto Japan, April 2007.
7. Collins JF, Zihua Hu. Microarray Analysis of Rat Duodenum during Iron- and Copper Deficiency. Poster presented at Experimental Biology, WashingtonD.C. April 2007.
8. Browne RW, Zihua Hu. Arachidonate 12-Lipoxygenase Is Strongly Induced by Iron-Deficiency and Is Expressed in Rat Small Intestine and Colon. Poster presented at Digestive Disease Week Meeting, WashingtonD.C.May 2007.
9. Collins JF and Zihua Hu(2006) Identification of Putative Transcriptional Regulatory Pathways Mediating the Genomic Response to Iron-deficiency in Rat Duodenum. Gastroenterology130:A540.
10. Collins JF, Zihua Hu, S Rakka, E Kilcourse and KV Kowdley (2006) Novel Differentially Expressed Genes Revealed by Microarray Analysis of Duodenum in Patients with Disorders of Iron Homeostasis. Oral abstract presentation. Digestive Disease Week Annual Meeting, Los Angeles,CA.
11. Zihua Hu, Collins JF. Copper Deprivation Results in Alterations in Intestinal Gene Expression Distinct From Those Caused By Iron-Deficiency. Poster presented at the 6^th International Copper Meeting. Alghero, Sardinia,Italy, October, 2006.
12. Ravia JJ, RM Stephen, Zihua Hu, LM Garrick, MD Garrick and JF Collins (2005) Microarray Analyses Reveal Unique Gene Expression Patterns in The Intestinal Mucosa of DMT1-deficient, Belgrade Rats. Book of Abstracts, International BioIron Society, 94: p223

Source: NIH                      2R01EY019949                Period: 09/2015 – 08/2019    

Title: ER Stress and Diabetic Retinopathy

PI: Xin Zhang                                                                         

Major Goals: Diabetic retinopathy (DR), a major complication of diabetes, is a leading cause of vision impairment and loss in the working age population. The goals are to delineate the role of endoplasmic reticulum (ER) stress in the development of retinal vascular pathology in diabetes, and to test the therapeutic potential of a novel protective agent in counteracting ER stress and inflammatory damage of retinal cells in DR. The realization of these goals is anticipated to identify a novel mechanism underpinning the retinal complications of diabetes and pave the way for new therapies to prevent/treat this sight-threatening disease

Role: Co-investigator

Source: NIH (NCI)            1U01CA175315                    Period: 04/2014 – 03/2019

Title: microRNA-1291 IN regulation of xenobiotic disposition and cell differentiation

PI: Aiming Yu                                                                         

Major Goals: The study is to delineate the mechanistic functions of miR-1291 in the regulation of drug disposition and endobiotics homeostasis and to define its roles and molecular in the control of cancer cell proliferation, invasion, and tumor progression processes. The final goal is to establish the effectiveness and safety profiles of miR-1291 therapeutics in clinically relevant animal models

Role: Co-investigator

Source: NIH                      R01 AI061580 06A1               Period: 04/2012 – 03/2017

Title: Regulation of RNA editing in Trypanosoma Brucei

PI: Laurie Read                                                                      

Major Goals: To reveal the molecular mechanisms of RNA editing in kinetoplastid parasites. The RNA editing event is unique to kinetoplastids and absent from their human hosts
Role: Co-investigator

Source: NIH                      1R21HD075218                      Period: 04/2014 – 03/2016    

Title: Trophoblasts and Inflammation: An Epigenetic Approach

PI: Jim Jarvis                                                                         

Major Goals: To characterize genome-wide methylation patterns in term chorionic trophoblasts in an in vitro model of inflammation using two complementary, sequencing-based methods, and to perform genome-wide analysis of the trophoblast transcriptome in this same model, examining expressed genes, splice variants, and non-coding transcripts that may affect the physiologic response of the trophoblast to inflammation

Role: Co-investigator

Source: NIH                      1R01EY020545                      Period: 04/2011 – 03/2016

Title: Interaction of Isl1 and Pou4f2 in retinal development

PI: Xiuqiqn Mu                                                                       

Major Goals: The overall goal is to understand how two transcription factors, Isl1 and Pou4f2, interact and regulate gene expression during the development of retinal ganglion cells. This will further our understanding of the structure and logic of the gene regulatory network underlying the specification and differentiation of retinal ganglion cells which are critical for vision.

Role: Co-investigator

Source: NSF                                                                 Period: 03/2011 – 02/2015

Title: The role of protein arginine methylation in the co-transcriptional recruitment of pre-mRNA splicing factors

PI: Michael Yu                                                                        

Major Goals: The overall goals of this project are to examine the mechanisms by which protein arginine methylation modulates the co-transcriptional recruitment of splicing factors in the simple eukaryotic model organism Saccharomyces cerevisiae. A combination of molecular biology, biochemistry, proteomic, and genomic methodologies will be used.

Role: Co-investigator

Source: NIH                      1R01AI0855690                    Period: 09/2009 – 08/2011

Title: Integration of Clinical, Genomic and Proteomic Data In HIV-1 using a Bioinformatic Approach

PI: Stanley Schwartz                                                                         

Major Goals: The overall goal of this study is the integration of the clinical, genomic and proteomic data derived from unique HIV-1 patient cohorts using bioinformatics to yield a comprehensive database from which to predict patient outcomes and responses to therapy.

Role: Co-investigator

Source: NIH                      5R01AI028304                      Period: 01/2005 – 12/2010

Title: Development of a Vaccine for Moraxella Catarrhalis

PI:Tim Murphy                                                                       

Major Goals: The overall goal of this proposal is to evaluate proteins as vaccine antigens and to use a powerful genomics approach to identify and study potential vaccine antigens for M. catarrhalis.

Role: Co-investigator

Source: NIH                                                                 Period: 01/2011 – 12/2011

Title: Pathogenesis of Haemophilus Influenza Infection in Copd

PI:Tim Murphy                                                                       

Major Goals: Persistence of nontypeable Haemophilus influenzae in the lower airways of adults with chronic obstructive pulmonary disease (COPD) causes airway inflammation and impaired pulmonary function. The goal of this proposal is to use state of the art methods to investigate how NTHI persists and the consequences of its persistence. The results will reveal new ways to eradicate persistent NTHI and have great potential for novel discoveries to prolong and improve the lives of people with COPD

Role: Co-investigator

Source: American Heart Association                             Period: 01/2008 – 12/2011

Title: The Role of Protein Arginine Methlation in Gene Expression

PI:Michale Yu                                                                         

Major Goals: The proposed studies are to provide valuable information for the elucidation of the role of protein arginine methylation in the control of gene expression relevant to their function in maintaining genome stability.

Role: Co-investigator

Source: RPCI                                                                Period: 09/2009 – 09/2019

Title: MicroRNA Targets in Immune Genes and the Dicer/Argonaute and ARE Machinery Components

Role: PI

Source: RPCI                                                                Period: 09/2010 – 09/2013

Title: Medical and biological data analysis and mining

Major Goal: The overall goal of this grant is to use computational and bioinformatics approaches to improve the understanding of cancer using data from both medical and biomedical research

Role: PI

Source: NIH                      5R01DK074867                      Period: 07/2007 – 06/2012

Title: Molecular Mechanisms of Intestinal Metal Ion Transport during Iron-Deficiency

PI: James Collin                                                                     

Major Goals: The overall goals are to determine the roles that Dmti and Atpya play in the induction of copper transport during iron-deprivation and to decipher the molecular mechanisms of induction of Dmti and Atpya during iron-deprivation.

Role: Co-investigator

Source: NSF                                                                  Period: 07/2004 – 07/2006

Title: Genome Sequencing of Plant-associated Azospirirllum brasilense

PI: Matthew Koffas                                                                            

Major Goals: The overall goal is to complete genome sequencing of A.  brasilense in order to gain insights into the biology of plant-microbe associations and the biochemistry of biosynthetic pathways for future advances in its agronomic and industrial applications.

Role: Co-investigator

Source: University at Buffalo                                       Period: 09/2008 – 08/2009

Title: MicroRNA Regulation of ABC Membrane transporters

PI: Aiming Yu                                                                         

Major Goals: The overall goal of this study is to understand the microRNA regulation on ABC membrane transporter related genes.

Role: Co-investigator

Source: General Mills                                                 Period: 04/2006 – 03/2008

Title: Effect of Dietary yogurt and Fiber on the Management of Intestinal Inflammation

PI: Shiu-Ming Kuo                                                                  

Major Goals: The overall goal is to use dietary factors to modulate inflammatory responses as a mean to manage gastrointestinal diseases

Role: Co-investigator

Spring 2010 - Instructor for "Introduction of Bioinformatics and Computational Biology" BCH519 for graduate students

Spring 2009 - Instructor for "Introduction of Bioinformatics and Computational Biology" BCH519 for graduate students

Spring 2008 -  Instructor for "Introduction of Bioinformatics and Computational Biology" BCH519 for graduate students

Spring 2007 - Instructor for "Introduction of Bioinformatics and Computational Biology" BCH519 for graduate studentS