Salil A. Lachke, Ph.D.

Teaching

Fall Semester: BISC401/BISC609: Molecular Biology of the Cell (Course Website available through Sakai)

Research Interests

Second only to mental illnesses, we largely fear losing our sense of sight (Horowitz et al. 1997, Cepko 2001).  Loss of vision is detrimental and can result from a functional compromise of various components of the eye.  However, opacification of the transparent lens – clinically termed cataract – remains the leading cause of blindness in the world.  Cataract affects over 77 million individuals and its incidence continues to rise with increase in human life expectancy.  Surgery remains the only treatment, carrying with it the risk of secondary cataract formation – an undesirable complication, especially in the elderly.  Therefore, strategies to prevent or delay the onset of this disease need to be designed, a challenge for which comprehensive understanding of the development and maintenance of this unique tissue is essential.

 
My laboratory uses systems-based approaches and animal models for the identification and functional elucidation of genes involved in organ development and disease. We have developed a bioinformatics-based approach termed iSyTE (integrated Systems Tool for Eye gene discovery, http://bioinformatics.udel.edu/Research/iSyTE) and have successfully used it to identify novel cataract genes and predict several uncharacterized genes with potential function in lens development.  Our goal is to characterize these candidate genes using data from human patients and animal models in combination with biochemical, molecular, cell biological and genomics-level approaches.  As an important step towards this goal, we have recently used iSyTE in combination with human and mouse genetics to highlight the involvement of TDRD7 (a post-transcriptional regulatory protein and RNA granule component) in lens differentiation and cataractogenesis (Lachke et al. 2011, Science 331:1571-76 Pubmed).  Our long-term goal is to deduce the gene regulatory networks (GRNs) that underlie organogenesis, which will need to be resolved in order to devise new regenerative therapies for diseases that affect these tissues.  Besides its clinical significance, we anticipate that insights gained from this research can potentially unveil basic regulatory principles relevant to the differentiation of other cell and tissue types.

Current Projects

Project 1:  Elucidate the function of cytoplasmic RNA granules in the lens.  iSyTE has predicted several uncharacterized lens-enriched components of RGs.  In this project, we seek to comprehensively define the different classes of RGs present in the developing lens.  We then aim to identify RNA targets of specific RG components and RNA binding proteins (RBPs) in the lens AEL and FCs.  This research is expected to make a major contribution to the field by generating binding motifs for several RBPs and by identifying their functional targets in the context of a developing tissue.

Project 2. Define the TDRD7 interactome and target RNAs in the lens.  In this project, we aim to characterize the total repertoire of differentially regulated RNAs (including mRNAs and small RNAs) in Tdrd7 null mutant lens by expression profiling.  We also aim to define the TDRD7 lens interactome by using well-established proteomics-based protocols to identify the protein binding partners of TDRD7.  Identification of the critical nodes interacting with TDRD7 should have significant impact in providing insight into the post-transcriptional control of gene expression in lens development.

Project 3: Building a Gene Regulatory Network (GRN) for the developing lens.  We aim to use computational prediction and chromatin immuno-precipitation (ChIP) coupled with expression analysis, protein binding microarrays, algorithms e.g. Lever and PhylCRM and transgenic mouse technology to identify the nodes and edges functional in the lens GRN.  In our efforts to build a comprehensive GRN for the developing lens we seek to determine the TFs and their target enhancers and the associated cis-Regulatory Modules (CRMs) that function to regulate lens expressed genes.

Research Group

Salil Lachke (PI, Faculty Mentor)

Anne Terrell (Research Associate II)

Deepti Anand (Postdoctoral Fellow)

Carrie Barnum (Graduate Student)

Archana Siddam (Graduate Student)

Smriti Agrawal (Graduate Student)

Soma Dash (Graduate Student)

Salma Al Saai (Graduate Student)

Julie Cowart (Graduate Student - Co-advisor)

Christine Dang (Undergraduate Student)

Shaili Patel (Undergraduate Student)

Sylvie Smith (Undergraduate Student)

Angela Chang (Undergraduate Student)

Selected Publications

  • Manthey AL, Lachke SA, Fitzgerald PG, Mason R, Scheiblin DA, Duncan MK. Loss of Sip1 leads to migration defects and retention of ectodermal markers during lens development. Mechanisms of Development 2014: 131:86-110 View in: Pubmed
  • Wolf L, Harrison W, Jie H, Xie Q, Xiao N, Sun J, Kong L, Lachke SA, Kuracha MR, Govindarajan V, Brindle PK, Ashery-Padan R, Beebe DC, Overbeek PA, Cvekl A. Histone modifications and cell fate determination: lens induction requires CBP and p300. Nucleic Acids Research 2013: 41(22):10199-10214 View in: Pubmed
  • Tran P, Lachke SA, Stottmann R. Toward a systems-level understanding of the hedgehog signaling pathway: defining the complex, robust and fragile. Wiley Interdiscip Rev Syst Biol Med. 2013: 5(1):83-100 View in: Pubmed
  • Jumlongras D*, Lachke SA*, O'Connell DJ, Aboukhalil A, Li X, Choe SE, Ho JWK, Turbe-Doan A, Robertson E, Olsen BR, Bulyk ML, Amendt BA, Maas RL. An evolutionary conserved enhancer regulates BMP4 expression in developing incisor and limb bud. PLoS ONE. 2012: 7(6):e38568 *Equal contribution View in: Pubmed
  • Lachke SA*, Ho JWK*, Kryukov GV*, O’Connell DJ, Aboukhalil A, Bulyk ML, Park PJ, Maas RL. iSyTE: integrated Systems Tool for Eye gene discovery. Invest Ophthalmol Visual Sci. 2012: 53:1617-1627. *Equal Conribution View in: PubMed Presented at ARVO 2012, Abstract #1726 was Highlighted in "Emerging Trends and Hot Topics" by members of the Annual Meeting Program Committee as representing the newest and most innovative research being conducted in the various specialties; Abstract selected among the top ~5% of ~7000 abstracts and presentations in the meeting, View here
  • Lachke SA*, Higgins A*, Inagaki M, Saadi I, Xi Q, Long M, Quade BJ, Talkowski ME, Gusella JF, Fujimoto A, Robinson ML, Yang Y, Duong QT, Shapira I, Motro B, Miyoshi J, Takai Y, Morton CC, Maas RL. The cell-adhesion gene PVRL3 is associated with congenital cataract. Human Genet. 2012: 131:235-250. *Equal Conribution View in: PubMed
  • Lachke SA*, Alkuraya FS*, Kneeland SC*, Ohn T, Aboukhalil A, Howell GR, Saadi I, Cavallesco R, Yue Y, Tsai AC, Nair KS, Cosma MI, Smith RS, Hodges E, Alfadhli SM, Al-Hajeri A, Shamseldin HE, Behbehani A, Hannon GJ, Bulyk ML, Drack AV, Anderson PJ, John SW, Maas RL. Mutations in the RNA granule component TDRD7 cause cataract and glaucoma.  Science. 2011: 331:1571-1576 (Research Article*Equal Conribution View in: PubMed
  • Kasaikina MV, Fomenko DE, Labunsky VM, Lachke SA, Qiu W, Moncaster JA, Zhang J, Wojnarowicz Jr MW, Kumar SN, Malinouskil M, Schweizer U, Tsuji PA, Carlson BA, Maas RL, Lou MF, Goldstein LE, Hatfield DL, Gladyshev VN. 15 kDa selenoprotein (Sep15) knockout mice reveal roles of Sep15 in redox homeostasis and cataract development.  J Biol Chem. 2011: 286(38):33203-33212. View in: PubMed
  • Lachke SA, and Maas RL RNA granules and cataract. Expert Rev Ophthalmol. 2011: 6:497-500 View in:  http://www.expert-reviews.com/doi/full/10.1586/eop.11.53?prevSearch=authorsfield%253A%2528Lachke%252C%2BSalil%2BA%2529&searchHistoryKey=
  • Lachke SA, Zhang X, Maas RL. Photoreceptor cell development regulation. Encyclopedia Life Sci. [John Wiley and Sons, Ltd: Chichester] 2010: Published June 19, DOI: 10.1002/9780470015902.a0000833.pub2 View in: http://www.els.net/WileyCDA/ElsArticle/refId-a0000833.html
  • Rowan S, Siggers T, Lachke SA, Yue Y, Bulyk ML, Maas RL. Precise temporal control of the eye regulatory gene Pax6 through enhancer binding site affinity. Genes Dev. 2010: 24:380-385 View in: PubMed Featured on Cover
  • Lachke SA*, Maas RL. Building the developmental oculome: systems biology in vertebrate eye development and disease. Wiley Interdiscip Rev Syst Biol Med.  2010: 2:305-323 Published online October 2, 2009 DOI: 10.1002/wsbm.59 *(Corresponding Author) View in: PubMed
  • Burdon KP, Hattersley K, Lachke SA, Laurie KJ, Maas RL, Mackey DA, Craig JE. Investigation of eight candidate genes on chromosome 1p36 for total congenital cataract. Mol Vision. 2008: 14:1799-1804 View in: PubMed
  • Donner AL, Lachke SA, Maas RL. Lens induction in vertebrates: variations on a conserved theme of signaling events. Sem Cell Dev Biol. 2006: 17(6):676-685 View in: PubMed
  • Brockert PJ*, Lachke SA*, Srikantha T, Pujol C, Galask R, Soll DR. Phenotypic switching and mating-type switching of Candida glabrata at sites of colonization. Infection Immun. 2003: 71(12):7109-7118 *Equal Conribution View in: PubMed
  • Lachke SA, Lockhart SR, Daniels KJ, Soll DR. Skin facilitates Candida albicans mating. Infection Immun. 2003: 71(9):4970-4976 View in: PubMed Recommended by Faculty of 1000 as an Exceptional new finding
  • Lachke SA, Srikantha T, Soll DR. The regulation of EFG1 in white-opaque switching in Candida albicans involves overlapping promoters. Mol Microbiol. 2003: 48(2):523-536 View in: PubMed
  • Srikantha T, Lachke SA, Soll DR. Three mating type-like loci in Candida glabrata. Euk Cell. 2003: 2(2):328-340 View in: PubMed Recommended by Faculty of 1000 as a new finding
  • Lachke SA, Joly S, Daniels K, Soll DR. Phenotypic switching and filamentation in Candida glabrata. Microbiology. 2002: 148(9):2661-2674 View in: PubMed Featured on Cover
  • Ghormade VS, Lachke SA, Deshpande MV. Dimorphism in Benjaminiella poitrasii: involvement of intracellular endochitinase and N-acetylglucosaminidase activities in the yeast-mycelium transition. Folia Microbiol. 2000: 45(3):231-238 View in: PubMed
  • Lachke SA, Srikantha T, Tsai LK, Daniels K, Soll DR. Phenotypic switching in Candida glabrata involves phase-specific regulation of the metallothionein gene MT-II and the newly discovered hemolysin gene HLP. Infection Immun. 2000: 68(2):884-895 View inPubMed
  • Kvaal C, Lachke SA, Srikantha T, Daniels K, McCoy J, Soll DR. Misexpression of the opaque-phase-specific gene PEP1 (SAP1) in the white phase of Candida albicans confers increased virulence in a mouse model of cutaneous infection. Infection Immun. 1999: 67(12):6652-6662 View inPubMed

Other Information

AWARDS
2005    D.C. Spriestersbach Prize                 The University of Iowa, Iowa City
2008    Post-doctoral Clinical Award             American Society of Human Genetics
2009    Research Excellence Award             Biomedical Research Institute and BWH
2010    Bettelheim Award                              International Society for Eye Research

2012    Pew Scholar                                      The Pew Charitable Trusts

CURRENT FUNDING
2011 - 2015

NIH/NEI, 1 R01 EY021505-01: Post-transcriptional control of gene expression in lens development
PI: Dr. David Beebe (Washington University-St. Louis)
PI: Dr. Salil Lachke (University of Delaware, Newark)

2012 - 2013

Fight For Sight: Function of small Maf transcriptional regulators in lens development and cataract
PI: Dr. Salil Lachke (University of Delaware, Newark)

2012 - 2014

UDRF, Inc: Tdrd7 function in mammalian eye development
PI: Dr. Salil Lachke (University of Delaware, Newark)

2012 - 2016

Pew Charitable Trusts: Post-transcriptional regulation in mammalian eye development
PI: Dr. Salil Lachke (University of Delaware, Newark)

Assistant Professor of Biological Sciences
Pew Scholar in Biomedical Sciences

Phone: (302) 831-3040

Fax: (302) 831-2281

Email: salil@udel.edu

Office: 236 Wolf Hall

Lab: 351 Wolf Hall

Address:
Department of Biological Sciences
Wolf Hall
University of Delaware
Newark, DE 19716

Education

  • B.Sc. - The University of Pune, India
  • M.Sc. - The University of Pune, India
  • Ph.D. - The University of Iowa, Iowa City
  • Postdoctoral - Harvard Medical School
  • Instructor - Harvard Medical School