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.

Watch a video summary of Dr. Lachke's research here.

Watch Dr. Lachke's lecture on the 2012 Nobel prize winning work of Dr. John Gurdon and Dr. Shinya Yamanaka here.

If you are an ARVO member, watch Dr. Lachke's presentation in the 2015 ARVO minisymposium "Integrated genomic networks in eye development and pathogenesis" here.

Research Group

Laboratory Members:

Salil Lachke (PI, Faculty Mentor)

Deepti Anand (Postdoctoral Fellow)

Archana Siddam (Graduate Student)

Soma Dash (Graduate Student)

Salma Al Saai (Graduate Student)

Sandeep Aryal (Graduate Student)

Julie Cowart (Graduate Student - Co-advisor with Drs. Cathy Wu and Abhyudai Singh)

Joshua Barton (Undergraduate Student)

Nathaniel Borders (Undergraduate Student)

Lachke Laboratory Alumni:

Anne Terrell (Research Associate II, 2013-2015) (Present: Preceptor, University of Delaware)

Carrie Barnum (Graduated with M.S. 2012-2015) (Present: Research Associate, University of Pennsylvania)

Smriti Agrawal (Graduated with M.S. 2012-2014) (Present: Doctoral Student, Baylor College of Medicine)

Christine Dang (Undergraduate Honors Thesis 2012-2014) (Present: M.D. Program, Sidney Kimmel Medical College at Thomas Jefferson University)

Shaili Patel (Undergraduate Senior Thesis 2013-2014) (Present: Research Associate, University of Pennsylvania)

Sylvie Smith (Undergraduate Student, Research 2014) (Present: Associate Laboratory Technician, WuXi AppTec)

Angela Chang (Undergraduate Student, Research 2014) (Present: Undergraduate Student, University of Pennsylvania)

Stephanie Waters (Research Associate II, 2011-2013) (Present: Associate Scientist, DuPont)

Selected Publications

  • 2016 (4)
  • Butali A, Busch T, Liu H, Eliason S, Anand D, Bullard S, Gowans L, Nidey N, Saadi I, Lachke SA, Zhu Y, Adeyemo A, Amendt B, Roscioli T, Cornell R, Murray J. Exome sequencing confirms the role of ARHGAP29 in mendelian orofacial clefting. PLoS Genetics 2016: In review
  • Anand D, Lachke SA. Systems biology of lens development: a paradigm for disease gene discovery in the eye. Experimental Eye Research 2016: Being revised
  • Zhang Y, Fan J, Ho JWK, Hu T, Kneeland SC, Sellarole MA, de Vries WN, Lachke SA, Lang RA, John SWM, Maas RL. Crim1 regulates integrin signaling in murine lens development. Development 2016: 143:356-366 View in: Pubmed
  • Audette DS, Anand D, So T, Rubenstein TB, Lachke SA, Lovicu FJ, Duncan MK. Prox1 and fibroblast growth factor receptors form a novel regulatory loop controlling lens fiber differentiation and gene expression. Development 2016: 143:318-328 View in: Pubmed
  • 2015 (4)
  • Dash S, Dang CA, Beebe DC, Lachke SA. Deficiency of the RNA binding protein Caprin2 causes lens defects and features of Peters anomaly. Developmental Dynamics 2015: 244:1313-1327 View in: Pubmed
  • Anand D, Agrawal SA, Siddam AD, Motohashi H, Yamamoto M, Lachke SA. An integrative approach to analyze microarray datasets for prioritiztion of genes relevant to lens biology and disease. Genomics Data 2015: 5:223-227 View in: Pubmed
  • Agrawal SA, Anand D, Siddam AD, Kakrana A, Dash S, Scheiblin DA, Dang CA, Terrell AM, Waters SM, Singh A, Motohashi H, Yamamoto M, Lachke SA. Compound mouse mutants of bZIP transcription factors Mafg and Mafk reveal a regulatory network of non-crystallin genes associated with cataract. Human Genetics 2015: 134(7):717-735 View in: Pubmed
  • Terrell AM, Anand D, Smith SF, Dang CA, Pathania M, Waters SM, Beebe DC, Lachke SA. Molecular characterization of mouse lens epithelial cell lines and their suitability for studying RNA granules and cataract genes. Experimental Eye Research 2015: 131:42-55 View in: Pubmed
  • 2014 (3)
  • Anchan RM, Lachke SA, Gerami-Naini B, Lindsey J, Ng N, Naber C, Nickerson M, Cavallesco R, Rowan S, Eaton JL, Xi Q, Maas RL. Pax6- and Six3-mediated induction of lens cell fate in mouse and human ES cells. PLoS ONE 2014: 9(12):e115106 View in: Pubmed
  • Manthey AL, Terrell AM, Lachke SA, Polson S, Duncan MK. Development of novel filtering criteria to analyze RNA-sequencing data obtained from the murine ocular lens during embryogenesis. Genomics Data 2014: 2:369-374 View in: Pubmed
  • 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
  • 2013 (2)
  • 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 Interdisciplinary Reviews: Systems Biology & Medicine 2013: 5(1):83-100 View in: Pubmed
  • 2012 (3)
  • 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. Investigative Ophthalmology & Visual Science 2012: 53:1617-1627. *Equal contribution 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 Genetics 2012: 131:235-250. *Equal contribution View in: PubMed
  • 2011 (3)
  • 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.  Journal of Biological Chemistry 2011: 286(38):33203-33212. View in: PubMed
  • Lachke SA, and Maas RL RNA granules and cataract. Expert Reviews of Ophthalmology 2011: 6:497-500 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 contribution View in: PubMed
  • 2010 (3)
  • Lachke SA, Zhang X, Maas RL. Photoreceptor cell development regulation. Encyclopedia of Life Sciences [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 & Development 2010: 24:380-385 View in: PubMed Featured on Cover *Equal contribution
  • Lachke SA*, Maas RL. Building the developmental oculome: systems biology in vertebrate eye development and disease. Wiley Interdisciplinary Reviews: Systems Biology & Medicine  2010: 2:305-323 Published online October 2, 2009 DOI: 10.1002/wsbm.59 *(Corresponding Author) View in: PubMed
  • 1999-2009 (10)
  • 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. Molecular 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. Seminars in Cell & Developmental Biology 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 & Immunity 2003: 71(12):7109-7118 *Equal contribution View in: PubMed
  • Lachke SA, Lockhart SR, Daniels KJ, Soll DR. Skin facilitates Candida albicans mating. Infection & Immunity 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. Molecular Microbiology 2003: 48(2):523-536 View in: PubMed
  • Srikantha T, Lachke SA, Soll DR. Three mating type-like loci in Candida glabrata. Eukaryotic 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 Microbiologica 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 & Immunity 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 & Immunity 1999: 67(12):6652-6662 View inPubMed

Other Information

AWARDS AND HONORS

2015 Frederick Bettelheim Award, National Foundation for Eye Research, Omaha, NE, USA

Awarded to 1 U.S. Lens Scientist biennially to attend the International Conference on the Lens

2015 Nominated by University of Delaware Provost Domenico Grasso for the 2016 Blavatnik Awards for Young Scientists, The New York Academy of Sciences, NY, USA

The Provost nominates 1 Scientist from the entire UD Life Sciences faculty for this competitive national award every year

2015 University of Delaware Research Foundation, Inc. Strategic Initiatives Award

2014 Senior Thesis Mentor Award, University of Delaware, Newark, DE, USA

Awarded to 1 Faculty at Univ. of Delaware Each Year for Excellence in Mentoring Undergraduate Senior Thesis Research

http://www.udel.edu/udaily/2014/may/senior-thesis-mentor-050714.html

2014 Knights Templar Eye Foundation, Inc. Pediatric Ophthalmology Career Starter Grant Award Competitive Renewal

Awarded to 9 Young Investigators in Vision Research Nationwide

2013 Kavli Frontiers of Science Fellow, The Kavli Foundation, Oxnard, CA, USA

Fellows are selected by a committee of US National Academy of Sciences members from among young researchers who have already made recognized contributions to science, including recipients of major national fellowships and awards and who have been identified as future leaders in science.

http://www.nasonline.org/programs/kavli-frontiers-of-science/frontiers-alumni/alumni-directory/salil-lachke.html

2013 Alcon Research Institute Young Researcher Grant Award

Awarded to 8 Young Investigators in Vision Research Worldwide

http://www.udel.edu/udaily/2013/apr/alcon-ophthalmology-040213.html

2013 Selected as Junior Member of the Alcon Research Institute, Forth Worth, TX, USA

2013 Knights Templar Eye Foundation, Inc. Pediatric Ophthalmology Career Starter Grant Award

Awarded to 19 Young Investigators in Vision Research Nationwide

http://www.udel.edu/udaily/2013/jun/infants-cataracts-061313.html

2012 Pew Scholar in Biomedical Sciences, The Pew Charitable Trusts, Philadelphia, PA, USA

Awarded to “22 of America’s Most Promising Scientists”

http://www.udel.edu/udaily/2012/jun/lachke-pew-scholar-061412.html

2012 Fight for Sight Grant-in-Aid Award, Fight for Sight, Inc. New York, NY, USA

Awarded to 5 Young Investigators in Vision Research Nationwide

http://www.fightforsight.org/portals/0/docs/2012_grantwinners.pdf

2012 University of Delaware Research Foundation, Inc. Award

Awarded to 11 UD Faculty

http://www.udel.edu/udaily/2012/jun/research-foundation-awards-061212.html

2010 Bettelheim Travel Fellowship, National Foundation for Eye Research, Omaha, NE, USA

Awarded to 1 young cataract researcher to participate in the XIX International Society for Eye Research Biennial Meeting

2009 Elected to Sigma Xi, full member Harvard Chapter

2009 BRI Research Excellence Award, Biomedical Research Institute and Brigham & Women’s Hospital, Boston, MA, USA

In recognition of Innovative Research

http://www.brighamandwomens.org/about_bwh/publicaffairs/news/publications/DisplayBulletin.aspx?articleid=4538

2008 Charles Epstein Trainee Research Award, American Society of Human Genetics

Excellence in Post-doctoral Clinical Research” Awarded to top ~1% from 100+ of national and international applicants

http://www.ashg.org/pages/awards_pastrecipients.shtml

2005 D.C. Spriestersbach Prize, The University of Iowa in recognition of “Excellence in Doctoral Research”

Best Doctoral Dissertation in Life Sciences at the University of Iowa between the years 2003-2005; Awarded to one doctoral student within the entire Life Science community at University of Iowa every two years

http://www.grad.uiowa.edu/awards/past-spriesterbach-winners

2003 Developmental Studies Hybridoma Bank Sponsored Graduate Assistantship, The University of Iowa, Iowa City, IA, USA

2002 Award for Top Presentation, Jakobsen Graduate Student Forum, The University of Iowa, Iowa City, IA, USA

1999 Graduate Trainee Travel Award, American Society of Microbiology

1997 Scholarship Award, Sakal India Foundation, Pune, Maharashtra, India

“For pursuing graduate studies overseas

 

Articles in the University of Delaware community regarding research in the Lachke laboratory:

1.   http://www.udel.edu/udaily/2012/jun/lachke-pew-scholar-061412.html

2.   http://www.udel.edu/udaily/2012/jun/research-foundation-awards-061212.html

3.   http://www.udel.edu/udaily/2013/oct/undergraduate-science-102612.html

4.   http://www.udel.edu/udaily/2013/nov/nobel-lectures-110512.html

5.   http://www.udel.edu/udaily/2013/apr/alcon-ophthalmology-040213.html

6.   http://www.udel.edu/udaily/2013/jun/infants-cataracts-061313.html

7.   http://www.udel.edu/udaily/2013/may/grad-student-forum-052013.html

8.   http://www.udel.edu/udaily/2014/oct/research-recognition-103113.html

9.   http://www.udel.edu/udaily/2014/may/senior-thesis-mentor-050714.html

10. http://www.udel.edu/udaily/2014/jun/vision-research-061014.html

11. http://www.udel.edu/udaily/2015/aug/eye-research-081314.html

12. http://www.udel.edu/udaily/2015/jun/genetics-cataracts-061715.html

13. http://www.udel.edu/udaily/2016/oct/undergraduateresearch100615.html

14. http://www.udel.edu/udaily/2016/nov/cleft-related-genes-112315.html

15. http://www.udel.edu/udmessenger/vol20no3/stories/research-awards.html

16. http://www.udel.edu/udmessenger/vol21no4/stories/otg-honors-and-achievements.html

17. http://www.udel.edu/udmessenger/vol23no2/stories/faculty-lachke.html

FUNDING

 

RESEARCH HIGHLIGHTS