Resume

• 2001

  PhD

  Genetics

• 2000

  University of Cambridge

  Mapped single nucleotide polymorphisms along the second chromosome in Drosophila.

  University of Cambridge

  Summer Undergraduate Research in Stock Lab

  Center for Advanced Biotechnology and Medicine

  Summer undergraduate research studying protein structure of CheB

  a protein involved in bacterial chemotaxis.

  UMDNJ

  Graduate Research in the Winston Lab

  Department of Genetics

  PhD thesis research examining long-range enhancer/promoter interactions in the yeast Saccharomyces cerevisiae.

  Harvard Medical School

  Assistant Professor of Biology

  Teaching and research

  Baruch College

  Society for Developmental Biology

  Association for Women in Science

  National Postdoctoral Association

  Genetics Society of America

  Postdoctoral Advisory Representative to the Board of Directors

  English

  German

  National Science Foundation Predoctoral Fellowship

  2003-2006

  National Science Foundation

  DeLill Nasser Award for Professional Development in Genetics

  NIH Ruth L. Kirschstein-National Research Service Award Postdoctoral Fellowship

  2009-2012

  NIH-National Institute for Arthritis and Musculoskeletal and Skin Diseases

  Elected to Membership in Sigma Xi

  Princeton University

  Best Postdoctoral Talk

  New England Society for Developmental Biology Regional Meeting

• 1998

  Princeton University

  Undergraduate thesis research studying translational regulation of Nanos

  a protein required for proper anterior/posterior polarity in Drosophila embryonic development.

  Princeton University

  Research Associate

  Post-doctoral research at Memorial Sloan-Kettering Cancer Center examining the role gene regulation during muscle development in Drosophila.

  Memorial Sloan Kettering Cancer Center

  Assistant Professor in Molecular

  Cellular and Developmental Biology

  The Graduate Center

  City University of New York

  General Biology 1 Lab Instructor

  BIO101 Lab Instructor

  Fall Semester 2013

  Iona College

  Sarah Lawrence College

  Bronxville

  NY

  General Biology I: Genes

  Cells and Evolution

  Visiting Assistant Professor

• 1996

  AB

  Molecular Biology

  American Whig-Cliosophic Society\nPrinceton Model Congress

  Princeton University

• Mentoring

  Confocal Microscopy

  Gene Expression

  Editing

  Genetics

  Gene Regulation

  Biotechnology

  Drosophila

  Cell Biology

  Laboratory

  Biology

  Immunohistochemistry

  Developmental Biology

  real-time PCR

  Molecular Biology

  Molecular Cloning

  Grant Writing

  Chromatin

  Conference Presentations

  Fluorescence Microscopy

  Morphogenesis of the somatic musculature in Drosophila melanogaster

  Mary K. Baylies

  In Drosophila melanogaster

  the somatic muscle system is first formed during embryogenesis

  giving rise to the larval musculature. Later during metamorphosis

  this system is destroyed and replaced by an entirely new set of muscles in the adult fly. Proper formation of the larval and adult muscles is critical for basic survival functions such as hatching and crawling (in the larva)

  walking and flying (in the adult)

  and feeding (at both larval and adult stages). Myogenesis

  from mononucleated muscle precursor cells to multinucleated functional muscles

  is driven by a number of cellular processes that have begun to be mechanistically defined. Once the mesodermal cells destined for the myogenic lineage have been specified

  individual myoblasts fuse together iteratively to form syncytial myofibers. Combining cytoplasmic contents demands a level of intracellular reorganization that

  most notably

  leads to redistribution of the myonuclei to maximize internuclear distance. Signaling from extending myofibers induces terminal tendon cell differentiation in the ectoderm

  which results in secure muscle-tendon attachments that are critical for muscle contraction. Simultaneously

  muscles become innervated and undergo sarcomerogenesis to establish the contractile apparatus that will facilitate movement. The cellular mechanisms governing these morphogenetic events share numerous parallels to mammalian development

  and the basic unit of all muscle

  the myofiber

  is conserved from flies to mammals. Thus

  studies of Drosophila myogenesis and comparisons to muscle development in other systems highlight conserved regulatory programs of biomedical relevance to general muscle biology and studies of muscle disease.

  Morphogenesis of the somatic musculature in Drosophila melanogaster

  Mary K. Baylies

  Twist (Twi)

  a conserved basic helix-loop-helix transcriptional regulator

  directs the epithelial-to-mesenchymal transition (EMT)

  and regulates changes in cell fate

  cell polarity

  cell division and cell migration in organisms from flies to humans. Analogous to its role in EMT

  Twist has been implicated in metastasis in numerous cancer types

  including breast

  pancreatic and prostate. In the Drosophila embryo

  Twist is essential for discrete events in gastrulation and mesodermal patterning. In this study

  we derive a twi allelic series by examining the various cellular events required for gastrulation in Drosophila. By genetically manipulating the levels of Twi activity during gastrulation

  we find that coordination of cell division is the most sensitive cellular event

  whereas changes in cell shape are the least sensitive. Strikingly

  we show that by increasing levels of Snail expression in a severe twi hypomorphic allelic background

  but not a twi null background

  we can reconstitute gastrulation and produce viable adult flies. Our results demonstrate that the level of Twi activity determines whether the cellular events of ventral furrow formation

  EMT

  cell division and mesodermal migration occur.

  Discrete Levels of Twist Activity are Required to Direct Distinct Cell Functions During Gastrulation and Somatic Myogenesis

  Daniel St Johnston

  Sophie G. Martin

  Here we describe the development of a single-nucleotide polymorphism (SNP) map for chromosome arm 3R. The map contains 73 polymorphisms between the standard FRT chromosome

  and a mapping chromosome that carries several visible markers (rucuca)

  at an average density of one SNP per 370 kilobases (kb). Using this collection

  we show that mutants can be mapped to a 400 kb interval in a single meiotic mapping cross

  with only a few hundred SNP detection reactions. Discovery of further SNPs in the region of interest allows the mutation to be mapped with the same recombinants to a region of about 50 kb.

  A rapid method to map mutations in Drosophila

  Fred Winston

  Most fundamental aspects of transcription are conserved among eukaryotes. One striking difference between yeast Saccharomyces cerevisiae and metazoans

  however

  is the distance over which transcriptional activation occurs. In S. cerevisiae

  upstream activation sequences (UASs) are generally located within a few hundred base pairs of a target gene

  while in Drosophila and mammals

  enhancers are often several kilobases away. To study the potential for long-distance activation in S. cerevisiae

  we constructed and analyzed reporters in which the UAS-TATA distance varied. Our results show that UASs lose the ability to activate normal transcription as the UAS-TATA distance increases. Surprisingly

  transcription does initiate

  but proximally to the UAS

  regardless of its location. To identify factors affecting long-distance activation

  we screened for mutants allowing activation of a reporter when the UAS-TATA distance is 799 bp. These screens identified four loci

  SIN4

  SPT2

  SPT10

  and HTA1-HTB1

  with sin4 mutations being the strongest. Our results strongly suggest that long-distance activation in S. cerevisiae is normally limited by Sin4 and other factors and that this constraint plays a role in ensuring UAS-core promoter specificity in the compact S. cerevisiae genome.

  Analysis of transcriptional activation at a distance in Saccharomyces cerevisiae

  David Botstein

  Studies of natural populations of many organisms have shown that traits are often complex

  caused by contributions of mutations in multiple genes. In contrast

  genetic studies in the laboratory primarily focus on studying the phenotypes caused by mutations in a single gene. However

  the single mutation approach may be limited with respect to the breadth and degree of new phenotypes that can be found. We have taken the approach of isolating complex

  or polygenic mutants in the lab to study the regulation of transcriptional activation distance in yeast. While most aspects of eukaryotic transcription are conserved from yeast to human

  transcriptional activation distance is not. In Saccharomyces cerevisiae

  the upstream activating sequence (UAS) is generally found within 450 base pairs of the transcription start site (TSS) and when the UAS is moved too far away

  activation no longer occurs. In contrast

  metazoan enhancers can activate from as far as several hundred kilobases from the TSS. Previously

  we identified single mutations that allow transcription activation to occur at a greater-than-normal distance from the GAL1 UAS. As the single mutant phenotypes were weak

  we have now isolated polygenic mutants that possess strong long-distance phenotypes. By identification of the causative mutations we have accounted for most of the heritability of the phenotype in each strain and have provided evidence that the Mediator coactivator complex plays both positive and negative roles in the regulation of transcription activation distance.

  Analysis of Polygenic Mutants Suggests a Role for Mediator in Regulating Transcriptional Activation Distance in Saccharomyces cerevisiae

  Mary K. Baylies

  Myogenesis in Drosophila embryos requires fusion between Founder cells (FCs) and Fusion Competent myoblasts (FCMs) to form multinucleate myotubes. Myoblast fusion is well characterized in embryos

  and many factors required for this process have been identified; however

  a number of questions pertaining to the mechanisms of fusion remain and are challenging to answer in the embryo. We have developed a modified primary cell culture protocol to address these questions in vitro. Using this system

  we determined the optimal time for examining fusion in culture and confirmed that known fusion proteins are expressed and localized as in embryos. Importantly

  we disrupted the actin and microtubule networks with the drugs latrunculin B and nocodazole

  respectively

  confirming that actin is required for myoblast fusion and showing for the first time that microtubules are also required for this process in Drosophila. Finally

  we show that myotubes in culture adopt and maintain specific muscle identities.

  Characterization of early steps in muscle morphogenesis in a Drosophila primary culture system

  Ram Kumar

  Susan Abmayr

  Mary K. Baylies

  Drosophila\nMidline (Mid) is an ortholog of vertebrate Tbx20

  which plays roles in the\ndeveloping heart

  migrating cranial motor neurons and endothelial cells. Mid functions in cell\nfate specification and differentiation of tissues that include the ectoderm

  cardioblasts

  \nneuroblasts

  and egg chambers; however

  a role in the somatic musculature has not been\ndescribed. We identified\nmid\nin genetic and molecular screens for factors contributing to somatic\nmuscle morphogenesis. Mid is expressed in founder cells (FCs) for several muscle fibers

  and\nfunctions cooperatively with the T-box protein H15 in lateral oblique muscle 1 and the segment\nborder muscle. Mid is particularly important for the specification and development of the lateral\ntransverse (LT) muscles LT3 and LT4

  which arise by asymmetric division of a single muscle\nprogenitor. Mid is expressed in this progenitor and its two sibling FCs

  but is maintained only in\nthe LT4 FC. Both muscles were frequently missing in\nmid\nmutant embryos

  and LT4-associated\nexpression of the transcription factor Krüppel (Kr) was lost. When present

  LT4 adopted an LT3-\nlike morphology. Coordinately

  \nmid\nmis\nexpression caused LT3 to adopt an LT4-like morphology\nand was associated with ectopic Kr expression. From these data

  we concluded tha\nt\nmid\nfunctions\nfirst in the progenitor to direct development of LT3 and LT4

  and later in the FCs to influence\nwhich of these differentiation profiles is selected. Mid is the first T-box factor shown to\ninfluence LT3 and LT4 muscle identity and

  along with the T-box protein Optomotor-blind-\nrelated-gene-1 (Org-1) is representative of a new class of transcription factors in muscle\nspecification.

  Muscle cell fate choice requires the T-box transcription factor Midline in Drosophila

  Elizabeth R. Gavis

  Heather K. Duchow

  Ana N. Vlasak

  Ira E. Clark

  Translational repression of maternal nanos (nos) mRNA by a cis-acting Translational Control Element (TCE) in the nos 3'UTR is critical for anterior-posterior patterning of the Drosophila embryo. We show

  through ectopic expression experiments

  that the nos TCE is capable of repressing gene expression at later stages of development in neuronal cells that regulate the molting cycle. Our results predict additional targets of TCE-mediated repression within the nervous system. They also suggest that mechanisms that regulate maternal mRNAs

  like TCE-mediated repression

  may function more widely during development to spatially or temporally control gene expression.

  A common translational control mechanism functions in axial patterning and neuroendocrine signaling in Drosophila

  Mary K. Baylies

  The somatic muscle system formed during Drosophila embryogenesis is required for larvae to hatch

  feed

  and crawl. This system is replaced in the pupa by a new adult muscle set

  responsible for activities such as feeding

  walking

  and flight. Both the larval and adult muscle systems are comprised of distinct muscle fibers to serve these specific motor functions. In this way

  the Drosophila musculature is a valuable model for patterning within a single tissue: while all muscle cells share properties such as the contractile apparatus

  properties such as size

  position

  and number of nuclei are unique for a particular muscle. In the embryo

  diversification of muscle fibers relies first on signaling cascades that pattern the mesoderm. Subsequently

  the combinatorial expression of specific transcription factors leads muscle fibers to adopt particular sizes

  shapes

  and orientations. Adult muscle precursors (AMPs)

  set aside during embryonic development

  proliferate during the larval phases and seed the formation of the abdominal

  leg

  and flight muscles in the adult fly. Adult muscle fibers may either be formed de novo from the fusion of the AMPs

  or are created by the binding of AMPs to an existing larval muscle. While less is known about adult muscle specification compared to the larva

  expression of specific transcription factors is also important for its diversification. Increasingly

  the mechanisms required for the diversification of fly muscle have found parallels in vertebrate systems and mark Drosophila as a robust model system to examine questions about how diverse cell types are generated within an organism.

  Specification of the somatic musculature in Drosophila

  Mary K. Baylies

  Marc S. Halfon

  Skeletal muscles are formed in numerous shapes and sizes

  and this diversity impacts function and disease susceptibility. To understand how muscle diversity is generated

  we performed gene expression profiling of two muscle subsets from Drosophila embryos. By comparing the transcriptional profiles of these subsets

  we identified a core group of founder cell-enriched genes. We screened mutants for muscle defects and identified functions for Sin3A and 10 other transcription and chromatin regulators in the Drosophila embryonic somatic musculature. Sin3A is required for the morphogenesis of a muscle subset

  and Sin3A mutants display muscle loss and misattachment. Additionally

  misexpression of identity gene transcription factors in Sin3A heterozygous embryos leads to direct transformations of one muscle into another

  whereas overexpression of Sin3A results in the reverse transformation. Our data implicate Sin3A as a key buffer controlling muscle responsiveness to transcription factors in the formation of muscle identity

  thereby generating tissue diversity.

  Whole Genome Analysis of Muscle Founder Cells Implicates the Chromatin Regulator Sin3A in Muscle Identity

  Krista C.

  Dobi

  Iona College

  Harvard Medical School

  Memorial Sloan Kettering Cancer Center

  Baruch College

  The Graduate Center

  City University of New York

  UMDNJ

  Sarah Lawrence College