Marc S. Halfon PhD
Marc S. Halfon
PhD
Professor
Jacobs School of Medicine & Biomedical Sciences
Specialty/Research Focus
Bioinformatics; Biomedical Informatics; Cell growth, differentiation and development; Computational Biology; Developmental Biology; Gene Expression; Genomics and proteomics; Molecular and Cellular Biology; Molecular genetics; Signal Transduction; Transcription - Gene; Transgenic organisms
Professional Summary:
Research in my laboratory investigates the genetic regulatory circuitry that controls how cell fates are determined during development. We focus on two key aspects, intercellular signaling and transcriptional regulation, using primarily the fruit fly Drosophila melanogaster due to its extremely well-annotated genome and amenability to experimental manipulation. All conclusions, however, are expected to relate directly to mammalian (including human) gene regulation. Recently, we have also started investigating the regulatory genomics of other insect species of both medical and agricultural importance, beginning with the development of methods for regulatory element discovery in species with fully sequenced genomes but little functional, experimental data.
A defining feature of my laboratory is that it takes both wet-lab and computational/bioinformatics approaches to studying the same set of problems about development and transcriptional regulation; hypotheses and ideas generated using one set of methods are tested and explored using the other. Current research in the laboratory falls into two main areas: 1) discovery and characterization of transcriptional cis-regulatory modules (CRMs), and 2) mechanisms of specificity for receptor tyrosine kinase (RTK) signaling. The combined results of these studies will provide insight into gene regulation, genome structure, intercellular signaling, and the regulatory networks that govern embryonic development.
My group is also heavily involved in biocuration through our development and maintenance of REDfly, an internationally-recognized curated database of known Drosophila transcriptional cis-regulatory modules (CRMs) and transcription factor binding sites (TFBSs). Despite more than 25 years of experimental determination of these elements, the data have never been collected into a single searchable database. REDfly seeks to include all experimentally verified fly regulatory elements along with their DNA sequence, their associated genes, and the expression patterns they direct. REDfly is by far the most comprehensive database of regulatory elements for the higher eukaryotes and serves as an important resource for the fly and bioinformatics communities.
Education and Training:
- Fellowship, Developmental Biology & Bioinformatics, Harvard Medical School/Brigham & Women‘s Hospital (2003)
- PhD, Biology, Yale University (1998)
- MS, Biology, Yale University (1993)
- Biochemical Sciences, Harvard University, Magna Cum Laude (1991)
Employment:
- Professor, Biochemistry, University at Buffalo-SUNY Jacobs School of Medicine & Biomedical Sciences (2016-present)
- Adjunct Faculty, Molecular and Cellular Biology, Roswell Park Cancer Institute (2006-present)
- Adjunct Faculty, Biological Sciences, University at Buffalo-SUNY, Dept. of Biological Sciences Faculty of Arts and Letters (2006-present)
- Associate Professor, Biochemistry, University at Buffalo-SUNY Jacobs School of Medicine & Biomedical Sciences (2009–2015)
- Assistant Professor, Biochemistry, University at Buffalo-SUNY Jacobs School of Medicine & Biomedical Sciences (2003–2009)
Awards and Honors:
- Sustained Achievement Award- Exceptional Scholar Program (2020)
- Editor's choice "Best in Trends" paper (2020)
- Teaching Innovation Award (UB) (2011)
- American Cancer Society Research Scholar (2009)
Research Expertise:
- bioinformatics
- model system genetics
- regulatory genomics
- transcriptional regulation
Research Centers:
- Center of Excellence in Bioinformatics and Life Sciences
UB 2020 Strategic Strengths:
- Information and Computing Technology
- Molecular Recognition in Biological Systems and Bioinformatics
Grants and Sponsored Research:
- September 2021–August 2024
REDfly: The regulatory element database for Drosophila and other insects
NIH/NIGMS
Role: Principal Investigator
$1,415,154 - September 2021–August 2023
Measuring functional similarity between transcriptional enhancers using deep learning
NIH/NHGRI
Role: Co-Investigator
$118,818 - September 2019–August 2023
Mechanisms of Gene Regulatory Network Evolution
NSF
Role: Principal Investigator
$1,106,456 - June 2019–May 2023
Regulatory Element Discovery in Sequenced Insect Species
USDA
Role: Principal Investigator
$445,911 - September 2018–August 2021
ABI Sustaining: The REDfly database of transcriptional regulatory elements
NSF
Role: Principal Investigator
$446,544 - January 2016–December 2019
REDfly: The regulatory element database for Drosophila and other insects
NIGMS
Role: Principal Investigator
$1,221,000 - June 2016–May 2018
Regulatory element discovery in Anopheles gambiae
NIH
Role: Principal Investigator
$449,039 - September 2014–August 2017
ABI Sustaining: The REDfly database of transcriptional regulatory elements
National Science Foundation
Role: Principal Investigator
$447,398 - March 2012–February 2017
Regulatory element discovery in sequenced insect species
USDA
Role: Principal Investigator
$462,000 - July 2008–June 2013
High Sensitivity Discovery of Cis-Regulatory Modules
NIH/NIGMS
Role: Co-Principal Investigator
$1,700,000 - January 2009–December 2012
Mechanisms for Specificity in Receptor Tyrosine Kinase Signaling
American Cancer Society
Role: Principal Investigator
$700,000 - August 2009–July 2012
The REDfly Database of Transcriptional Regulatory Elements
National Science Foundation
Role: Principal Investigator
$524,049 - December 2009–November 2010
Integrated multi-dimensional genomic analysis of therapy related acute myeloid leukemia
New York State Center of Excellence in Bioninformatics & Life Sciences
Role: Co-Principal Investigator
$60,000 - December 2008–November 2009
Computational Identification of Transcription Factor Binding Sites
SUNY at Buffalo Interdisciplinary Research Development Fund
Role: Co-Principal Investigator
$27,000 - July 2006–July 2009
Nutrigenomics for the Study of Disease Prevention and Intervention
USDA
Role: Co-Investigator
$36,500 - March 2007–February 2009
Empirical Assessment of Analysis Methods for DNA Microarrays
NIH/NLM
Role: Principal Investigator
$79,250 - February 2006–September 2008
Genomic and Bioinformatic Approaches to Understanding Animal Development
NASA
Role: Consultant
$125,000 - July 2002–June 2008
Computational and Functional Analysis of Gene Networks
NIH/NHGRI
Role: Principal Investigator
$1,300,000 - September 2005–July 2006
Computational Approaches to Disease Causes and Treatment
NIH/NIGMS
Role: Co-Investigator
$20,000
Journal Articles:
- Reid, W., Sterling-Letnsch, G. and Halfon, M.S. (2023) Protocol for fixing and peeling Aedes aegypti embryos. protocols.io (Dec) doi:10.17504/protocols.io.261ged88wv47/v1
- Dyer NA, Lucas ER, Nagi SC, McDermott D, Brenas JH, Miles A, Clarkson CS, Mawejje HD, Wilding CS, Halfon MS, Asma H, Heinz E, Donnelly MJ. (2023) Mechanisms of transcriptional regulation in Anopheles gambiae revealed by allele specific expression. bioRxiv : the preprint server for biology (Nov). doi:10.1101/2023.11.22.568226
- Schember, I. , Reid, W. and Halfon, M.S. (2023) Conserved and novel enhancers regulate expression of Aedes aegypti single-minded in the embryonic ventral midline. BioRXiv (Aug) doi:10.1101/2023.08.01.551414.
- Garza AB, Garcia R, Halfon MS, Girgis HZ. (2023) Evaluation of metric and representation learning approaches: Effects of representations driven by relative distance on the performance. 2023 Intelligent Methods, Systems, and Applications (Jul), 2023: 545-550. doi:10.1109/imsa58542.2023.10217475
- Weinstein ML, Jaenke CM, Asma H, Spangler M, Kohnen KA, Konys CC, Williams ME, Williams AV, Rebeiz M, Halfon MS, Williams TM. (2023) A novel role for trithorax in the gene regulatory network for a rapidly evolving fruit fly pigmentation trait. PLoS genetics (Feb), 19(2): e1010653.
- Lindhorst D, Halfon MS. (2023) Reporter gene assays and chromatin-level assays define substantially non-overlapping sets of enhancer sequences. BMC genomics (Jan), 24(1): 17. doi:10.1186/s12864-023-09123-9
- Keränen SVE, Villahoz-Baleta A, Bruno AE, Halfon MS. (2022) REDfly: An Integrated Knowledgebase for Insect Regulatory Genomics. Insects (Jul), 13(7). doi:10.3390/insects13070618
- Schember I, Halfon MS. (2022) Common Themes and Future Challenges in Understanding Gene Regulatory Network Evolution. Cells (Feb), 11(3). doi:10.3390/cells11030510
- Asma H, Halfon MS. (2021) Annotating the Insect Regulatory Genome. Insects (Jun), 12(7). doi:10.3390/insects12070591
- Schember I, Halfon MS. (2021) Identification of new Anopheles gambiae transcriptional enhancers using a cross-species prediction approach. Insect molecular biology (Apr).
- Nowling RJ, Behura SK, Halfon MS, Emrich SJ, Duman-Scheel M. (2021) PeakMatcher facilitates updated Aedes aegypti embryonic cis-regulatory element map. Hereditas (Jan), 158(1): 7. doi:10.1186/s41065-021-00172-2
- Sinha S, Jones BM, Traniello IM, Bukhari SA, Halfon MS, Hofmann HA, Huang S, Katz PS, Keagy J, Lynch VJ, Sokolowski MB, Stubbs LJ, Tabe-Bordbar S, Wolfner MF, Robinson GE. (2020) Behavior-related gene regulatory networks: A new level of organization in the brain. Proceedings of the National Academy of Sciences of the United States of America (Sep), 117(38): 23270-23279. doi:10.1073/pnas.1921625117
- Halfon MS. (2020) Silencers, Enhancers, and the Multifunctional Regulatory Genome. Trends in genetics : TIG (Mar), 36(3): 149-151. doi:10.1016/j.tig.2019.12.005
- Tomoyasu Y, Halfon MS. (2020) How to study enhancers in non-traditional insect models. The Journal of experimental biology (Feb), 223(Pt Suppl 1).
- Asma H, Halfon MS. (2019) Computational enhancer prediction: evaluation and improvements. BMC Bioinformatics (Apr), 20(1): 174-174.
- Zhou Y, Popadowski SE, Deutschman E, Halfon MS. (2019) Correction: Distinct roles and requirements for Ras pathway signaling in visceral versus somatic muscle founder specification (doi:Â 10.1242/dev.169003). Development (Feb), 146(4).
- Kazemian M, Halfon MS. (2019) CRM Discovery Beyond Model Insects. Methods Mol Biol (Jan), 1858: 117-139.
- Rivera J, Keränen SVE, Gallo SM, Halfon MS. (2019) REDfly: the transcriptional regulatory element database for Drosophila. Nucleic Acids Res (Jan), 47(D1): 828-834.
- Zhou Y, Popadowski SE, Deutschman E, Halfon MS. (2019) Distinct roles and requirements for Ras pathway signaling in visceral versus somatic muscle founder specification. Development (Jan), 146(2).
- Halfon MS. (2019) Studying Transcriptional Enhancers: The Founder Fallacy, Validation Creep, and Other Biases. Trends Genet (Jan), 35(2): 93-103.
- Lai YT, Deem KD, Borrà s-Castells F, Sambrani N, Rudolf H, Suryamohan K, El-Sherif E, Halfon MS, McKay DJ, Tomoyasu Y. (2018) Enhancer identification and activity evaluation in the red flour beetle, Tribolium castaneum. Development (Jan), 145(7).
- Halfon MS. (2017) Perspectives on Gene Regulatory Network Evolution. Trends Genet (Jan), 33(7): 436-447.
- Suryamohan K, Hanson C, Andrews E, Sinha S, Scheel MD, Halfon MS. (2016) Redeployment of a conserved gene regulatory network during Aedes aegypti development. Dev Biol (Jun).
- Suryamohan K, Halfon MS. (2015) Identifying transcriptional cis-regulatory modules in animal genomes. Wiley Interdiscip Rev Dev Biol (Mar), 4(2): 59-84.
- Kazemian M, Suryamohan K, Chen JY, Zhang Y, Samee MA, Halfon MS, Sinha S. (2014) Evidence for deep regulatory similarities in early developmental programs across highly diverged insects. Genome Biol Evol (Sep), 6(9): 2301-2320.
- Dobi KC, Halfon MS, Baylies MK. (2014) Whole-genome analysis of muscle founder cells implicates the chromatin regulator Sin3A in muscle identity. Cell Rep (Aug), 8(3): 858-870.
- Atkinson TJ, Halfon MS. (2014) Regulation of gene expression in the genomic context. Comput Struct Biotechnol J (Jan), 9: 201401001-201401001.
- Halfon MS, Zhu Q, Brennan ER, Zhou Y. (2011) Erroneous attribution of relevant transcription factor binding sites despite successful prediction of cis-regulatory modules. BMC Genomics (Nov), 12: 578-578.
- Kazemian M, Zhu Q, Halfon MS, Sinha S. (2011) Improved accuracy of supervised CRM discovery with interpolated Markov models and cross-species comparison. Nucleic Acids Res (Aug).
- Tu C, Li J, Young R, Page BJ, Engler F, Halfon MS, Canty JM, Qu J. (2011) Combinatorial peptide ligand library treatment followed by a dual-enzyme, dual-activation approach on a nanoflow liquid chromatography/orbitrap/electron transfer dissociation system for comprehensive analysis of swine plasma proteome. Anal Chem (Jun), 83(12): 4802-4813.
- Zhu Q, Miecznikowski JC, Halfon MS. (2011) A wholly defined Agilent microarray spike-in dataset. Bioinformatics (May), 27(9): 1284-1289.
- Tu C, J Li, R Young, BJ page, F. Engler, MS Halfon, JM Canty Jr. and J Qu. (2011) Combinatorial peptide ligand library treatment followed by a dual-enzyme, dual-activation approach on a nanoflow liquid chromatography/orbitrap/electron transfer dissocation system for comprehensive analysis of swine plasma proteome. Anal. Chem. (Jan), 2(2): 4802-4813.
- Gallo SM, Gerrard DT, Miner D, Simich M, Des Soye B, Bergman CM, Halfon MS. (2011) REDfly v3.0: toward a comprehensive database of transcriptional regulatory elements in Drosophila. Nucleic acids research (Jan), 39(Database issue): D118-23. doi:10.1093/nar/gkq999
- Escamilla-Hernandez R, Chakrabarti R, Romano R, Smalley K, Zhu Q, Lai W, Halfon MS, Buck MJ, Sinha S. (2010) Genome-wide search identifies Ccnd2 as a direct transcriptional target of Elf5 in mouse mammary gland. BMC Mol Biol (Sep), 11: 68-68.
- Zhu Q, Miecznikowski JC, Halfon MS. (2010) Preferred analysis methods for Affymetrix GeneChips. II. An expanded, balanced, wholly-defined spike-in dataset. BMC Bioinformatics (May), 11: 285-285.
- Kantorovitz MR, Kazemian M, Kinston S, Miranda-Saavedra D, Zhu Q, Robinson GE, Göttgens B, Halfon MS, Sinha S. (2009) Motif-blind, genome-wide discovery of cis-regulatory modules in Drosophila and mouse. Developmental cell (Oct), 17(4): 568-79. doi:10.1016/j.devcel.2009.09.002
- Leatherbarrow JR, Halfon MS. (2009) Identification of receptor-tyrosine-kinase-signaling target genes reveals receptor-specific activities and pathway branchpoints during Drosophila development. Genetics (Apr), 181(4): 1335-45. doi:10.1534/genetics.108.098475
- Zhu Q, Halfon MS. (2009) Complex organizational structure of the genome revealed by genome-wide analysis of single and alternative promoters in Drosophila melanogaster. BMC genomics (Jan), 10: 9. doi:10.1186/1471-2164-10-9
- Yakoby N, Bristow CA, Gong D, Schafer X, Lembong J, Zartman JJ, Halfon MS, Schüpbach T, Shvartsman SY. (2008) A combinatorial code for pattern formation in Drosophila oogenesis. Dev Cell (Nov), 15(5): 725-737.
- Griffith OL, Montgomery SB, Bernier B, Chu B, Kasaian K, Aerts S, Mahony S, Sleumer MC, Bilenky M, Haeussler M, Griffith M, Gallo SM, Giardine B, Hooghe B, Van Loo P, Blanco E, Ticoll A, Lithwick S, Portales-Casamar E, Donaldson IJ, Robertson G, Wadelius C, De Bleser P, Vlieghe D, Halfon MS, Wasserman W, Hardison R, Bergman CM, Jones SJ. (2008) ORegAnno: an open-access community-driven resource for regulatory annotation. Nucleic Acids Res (Jan), 36(Datab): 107-113.
- Ivan A, Halfon MS, Sinha S. (2008) Computational discovery of cis-regulatory modules in Drosophila without prior knowledge of motifs. Genome Biol (Jan), 9(1): 22-22.
- Halfon MS, Gallo SM, Bergman CM. (2008) REDfly 2.0: an integrated database of cis-regulatory modules and transcription factor binding sites in Drosophila. Nucleic Acids Res (Jan), 36(Datab): 594-598.
- Halfon MS, Arnosti DN. (2007) New tools, resources for gene regulatory analysis in Drosophila. Fly (Austin) (Mar), 1(2): 123-124.
- Li L, Zhu Q, He X, Sinha S, Halfon MS. (2007) Large-scale analysis of transcriptional cis-regulatory modules reveals both common features and distinct subclasses. Genome biology (Jan), 8(6): R101. doi:10.1186/gb-2007-8-6-r101
- Zhu Q, Halfon MS. (2007) Vector-dependent gene expression driven by insulated P-element reporter vectors. Fly (Austin) (Jan), 1(1): 55-56.
- Gallo SM, Li L, Hu Z, Halfon MS. (2006) REDfly: a Regulatory Element Database for Drosophila. Bioinformatics (Feb), 22(3): 381-383.
- Estrada B, Choe SE, Gisselbrecht SS, Michaud S, Raj L, Busser BW, Halfon MS, Church GM, Michelson AM. (2006) An integrated strategy for analyzing the unique developmental programs of different myoblast subtypes. PLoS Genet (Feb), 2(2): 16-16.
- Choe SE, Boutros M, Michelson AM, Church GM, Halfon MS. (2005) Preferred analysis methods for Affymetrix GeneChips revealed by a wholly defined control dataset. Genome Biol (Jan), 6(2): 16-16.
- Grad YH, Roth FP, Halfon MS, Church GM. (2004) Prediction of similarly acting cis-regulatory modules by subsequence profiling and comparative genomics in Drosophila melanogaster and D.pseudoobscura. Bioinformatics (Nov), 20(16): 2738-2750.
- Halfon MS, Gisselbrecht S, Lu J, Estrada B, Keshishian H, Michelson AM. (2002) New fluorescent protein reporters for use with the Drosophila Gal4 expression system and for vital detection of balancer chromosomes. Genesis (Sep), 34(1-2): 135-138.
- Halfon MS, Michelson AM. (2002) Exploring genetic regulatory networks in metazoan development: methods and models. Physiol Genomics (Sep), 10(3): 131-143.
- Halfon MS, Grad Y, Church GM, Michelson AM. (2002) Computation-based discovery of related transcriptional regulatory modules and motifs using an experimentally validated combinatorial model. Genome Res (Jul), 12(7): 1019-1028.
- Carmena A, Buff E, Halfon MS, Gisselbrecht S, Jiménez F, Baylies MK, Michelson AM. (2002) Reciprocal regulatory interactions between the Notch and Ras signaling pathways in the Drosophila embryonic mesoderm. Dev Biol (Apr), 244(2): 226-242.
- Halfon MS, Carmena A, Gisselbrecht S, Sackerson CM, Jiménez F, Baylies MK, Michelson AM. (2000) Ras pathway specificity is determined by the integration of multiple signal-activated and tissue-restricted transcription factors. Cell (Sep), 103(1): 63-74.
- Halfon MS, Keshishian H. (1998) The Toll pathway is required in the epidermis for muscle development in the Drosophila embryo. Dev Biol (Jul), 199(1): 164-174.
- Halfon MS, Kose H, Chiba A, Keshishian H. (1997) Targeted gene expression without a tissue-specific promoter: creating mosaic embryos using laser-induced single-cell heat shock. Proc Natl Acad Sci U S A (Jun), 94(12): 6255-6260.
- Halfon MS, Hashimoto C, Keshishian H. (1995) The Drosophila toll gene functions zygotically and is necessary for proper motoneuron and muscle development. Dev Biol (May), 169(1): 151-167.
- Tolias PP, Konsolaki M, Halfon MS, Stroumbakis ND, Kafatos FC. (1993) Elements controlling follicular expression of the s36 chorion gene during Drosophila oogenesis. Mol Cell Biol (Sep), 13(9): 5898-5906.
- Keshishian H, Chiba A, Chang TN, Halfon MS, Harkins EW, Jarecki J, Wang L, Anderson M, Cash S, Halpern ME. (1993) Cellular mechanisms governing synaptic development in Drosophila melanogaster. J Neurobiol (Jun), 24(6): 757-787.
Professional Memberships:
- Pan-American Society for Evolutionary Developmental Biology (2017–present)
- International Society for Biocuration (2010–present)
- International Society for Computational Biology (2005–present)
- Society for Developmental Biology (1998–present)
- Genetics Society of America (1995–present)
- AAAS (1993–present)
- Society for Neuroscience (1992–1997)
Presentations:
- "The regulatory genomes of class Insecta" Department seminar series, University of Dayton (2023)
- "Convergence and Divergence of Enhancer Sequences" Genetics Society (UK) symposium “Functional Regulatory Genomics and Disease” (2022)
Service Activities:
- ; Ad hoc reviewer for multiple (5-6) NIH, NSF panels (2023)
- i5k consortium (insect genomics); executive committee member (2023–present)
- ; ad hoc reviewer, multiple study sections (2022)
- journals including (inter alia): Bioinformatics; BMC Bioinformatics; BMC Genomics; Cell Reports; Critical Reviews In Biochemistry & Molecular Biology; Current Bioinformatics; Development; Developmental Biology; eLife; Fly; G3; Gene; Genetics; Genome Biology; Genome Research; Genomics; JoVE; Molecular Systems Biology; Nature Chemical Biology; Nature Communications; Nature Genetics; Nature Methods; Nucleic Acids Research; PLoS Biology; PLoS Computational Biology; PLoS Genetics; PLoS One; PNAS; Science; review for multiple journals (2021–present)
- NSF BIO/IOS; ad hoc reviewer (2021)
- JSMBS Promotions and Tenure Committee (tenurial ranks); member (2020–2023)
- JSMBS junior faculty mentoring committee; member (2019–present)
- MSTP Admissions Committee; member (2018–2022)
- Graduate Affairs Committee; member (2013–present)
- NIH; GCAT;; Ad Hoc Reviewer (2012–present)
- GCAT SEP; Special emphasis panel for GCAT;; Ad Hoc Reviewer (2011)
- Search committee, Bioinformatics; Committee Member (2011–2012)
- Search committee, Biomedical Engineering; Committee Member (2011)
- PPBS admissions committee; Committee Member (2009–2015)
- Search committee, OBGYN chair; Committee Member (2009–2010)
- American Cancer Society; Development, Differentiation and Cancer;; Panel Member (2008–2012)
- Health Science Library committee; Advisory Committee (2007–2014)
- Executive Committee, CCR; Advisory Committee (2005–2006)
- Search committee, BIO faculty hire in Cell Biology; Committee Member (2004–2005)
- IFR committee; member (2003–present)
- n/a; assorted external reviews for NSF;; External Reviewer (2003–present)