| 176 | Velia Fowler, Ph.D. | <p>Professor and Chair <br></p> | (302) 831-4296 | (302) 831-2281 | vfowler@udel.edu | 118 Wolf Hall | 341 Wolf Hall | Department of Biological Sciences 105 The Grn, 118 Wolf Hall, Newark, DE 19716 | <ul>
<li><strong>B.A.</strong> - Oberlin College, Oberlin, OH
</li><li><strong>Ph.D</strong>. - Harvard University, Cambridge, MA
</li><li>National Science Foundation Predoctoral Fellow
</li><li><strong>Postdoctoral </strong>- Jane Coffin Childs Postdoctoral Fellow, National Institutes of Health and Johns Hopkins University School of Medicine </li></ul> | | <p>The Fowler laboratory studies cellular architecture: how cells spatially organize themselves and their interior compartments to achieve intricate geometries, mechanical strength, and physiological functions. We have studied how cell architecture contributes to normal cell functions or dysfunction in disease for red blood cell shape and deformability, skeletal and cardiac muscle contraction, endothelial cell migration, megakaryocyte formation of platelets, epithelial cell shapes and eye lens transparency and mechanics. The basis of cellular architecture is the cytoskeleton, a collection of specialized and dynamic “building blocks” that act as a cell’s scaffolding. Our investigations into the cytoskeleton focus on structural elements known as actin and myosin filaments, with an emphasis on how these nanoscale components generate microscale cellular architecture and macroscale tissue and organ function. We are interested in how the cytoskeleton provides mechanical stability and produces contractile forces that shape membrane curvature and confer mechanical resilience during cell differentiation, morphogenesis and aging. Our approaches include biochemistry, biophysics, super-resolution fluorescence microscopy, mouse genetics and physiology, and analysis of human cells from patients with congenital diseases.<br></p> | <p><strong>1. Red Blood Cell Shape</strong></p>
<p>The biconcave disk shape and deformability of mammalian red blood cells (RBCs) rely upon the membrane skeleton, a viscoelastic network of short actin filaments interconnected by long spectrin tetramers in a periodic lattice. Unlike many other cell types, RBCs can be easily isolated in large quantities and contain no transcellular or cytoplasmic cytoskeleton, allowing the membrane skeleton to be studied in isolation from other populations of actin or myosin. Since periodic spectrin-actin networks are present in other cells, such as neurons and epithelial cells, the RBC membrane provides a unique paradigm for exploration of fundamental principles in membrane biology. Recently, our lab discovered that non-muscle myosin IIA (NMIIA) motors interact with the spectrin-actin network to maintain RBC biconcave shape and deformability. We are studying nanoscale lattice structure and NMIIA assembly using super-resolution fluorescence microscopy; membrane curvature and cell shape using 3D confocal microscopy; cell deformability using biomechanical assays; and physiology using hematological assays. By examining RBCs from human patients and transgenic mice with mutations in NMIIA or membrane skeleton components, we can reveal the molecular and structural basis of RBC shape, deformability, and physiology. We also collaborate with computational cell biologists to model how NMIIA forces exerted on the nanoscale network structure determine microscale membrane curvature and biconcave shapes.</p>
<p><a href="http://www.bloodjournal.org/content/116/14/2406">Read more about the spectrin-actin lattice here</a>.<br></p><p><a href="http://www.pnas.org/content/115/19/4813.long">Read more about myosin and RBC shape</a>.<br></p><p><a href="https://www.the-scientist.com/the-literature/how-red-blood-cells-get-their-dimples-64680">Read an article in “The Scientist” about Actomyosin and RBC shape</a>.<br></p>
<p><strong>2. Red Blood Cell Formation</strong></p>
<p>Biogenesis of mammalian RBCs (erythropoiesis) is a highly orchestrated process of terminal differentiation in which regulated gene expression directs a series of cell divisions coupled to dramatic changes in cell and nuclear morphology, culminating in cell cycle exit and nuclear expulsion (enucleation). While enucleation has been described morphologically for decades, the molecular mechanisms that drive the process remain unclear. We study erythroblast enucleation in hematopoietic organs (bone marrow, spleen, and fetal liver) from transgenic mice and in human hematopoietic stem cells with actin cytoskeleton mutations. We identify critical components by genetics, proteomics and biochemistry, analyze 3D cell shape and cytoskeleton architecture using confocal and super-resolution fluorescence microscopy, observe dynamics of fluorescent-tagged cellular components using time-lapse microscopy of living erythroblasts, and determine enucleation forces using computational modeling. These studies will elucidate molecular mechanisms of human congenital anemias due to defects in erythropoiesis and enucleation and provide strategies for optimizing RBC production <em>in vitro</em> for future applications in transfusion medicine.</p>
<p><a href="http://www.bloodjournal.org/content/123/5/601">Read more about the actin cytoskeleton and enucleation</a>.<br></p>
<p><strong>3. Eye Lens Function</strong></p>
<p>The lens functions to fine focus light onto the retina to produce a clear image. For proper functioning, the lens not only has to be clear but also must be an appropriate size, shape, and mechanical stiffness. Age-associated conditions of the lens include cataracts (lens cloudiness) and presbyopia (difficulty to focus on close objects). Despite decades of study, the exact mechanisms underpinning these aging conditions remain unclear. Using transgenic mice and other mammalian model systems combined with genomic, proteomic, and biochemical approaches, we aim to identify the actin cytoskeleton components that determine lens growth, cell sizes and shapes, and their microstructural mechanical responses. We utilize electron microscopy and high-and super-resolution fluorescence confocal microscopy to evaluate the complex 3-dimensional shapes and structures of lens cells. Additionally, by utilizing specialized equipment we mechanically compress or stretch lenses to evaluate biomechanical properties, and collaborate with engineers and computational biologists to model forces within the lens. This will enable us to understand how the actin cytoskeleton establishes lens size, shape, and biomechanical properties, and how cytoskeleton dysfunction may contribute to cataracts and/or presbyopia. <br></p>
| <p><br></p> | <p><a href="http://www.ncbi.nlm.nih.gov/sites/myncbi/velia.fowler.1/bibliography/40725557/public/?sort=date&direction=descending">Velia Fowler's Bibliography</a></p><p>
</p><p><strong>Last 5 years:</strong></p><p>
</p><p>Islam, S.T., Cheng, C., Parreno, J., <b>Fowler, V.M.</b>, 2023. Nonmuscle Myosin IIA Regulates the Precise Alignment of Hexagonal Eye Lens Epithelial Cells During Fiber Cell Formation and Differentiation.<em> Invest Ophthalmol. Vis. Sci.</em><b></b> 64, 20.<a href="https://doi.org/10.1167/iovs.64.4.20"> https://doi.org/10.1167/iovs.64.4.20</a> </p><p class="p2" style="margin-bottom:0px;font-feature-settings:normal;font-stretch:normal;font-size:11px;line-height:normal;font-family:helvetica;color:#000000;min-height:13px;"><br class="ms-rteThemeBackColor-1-0"></p><p>Ghosh, A., Coffin, M., West, R., <b>Fowler, V.M.</b>, 2022. Erythroid differentiation in mouse erythroleukemia cells depends on Tmod3-mediated regulation of actin filament assembly into the erythroblast membrane skeleton. <i>FASEB J.</i><u></u> 36, e22220.<a href="https://doi.org/10.1096/fj.202101011R"> https://doi.org/10.1096/fj.202101011R</a></p><p class="p1" style="margin-bottom:0px;font-feature-settings:normal;font-stretch:normal;font-size:11px;line-height:normal;font-family:helvetica;color:#000000;"><span class="Apple-converted-space ms-rteThemeBackColor-1-0"><br></span></p><p>Nowak, R.B., Alimohamadi, H., Pestonjamasp, K., Rangamani, P., <b>Fowler, V.M.</b>, 2022. Nanoscale dynamics of actin filaments in the red blood cell membrane skeleton. <i>Mol. Biol. Cell</i> 33, ar28.<a href="https://doi.org/10.1091/mbc.E21-03-0107"> https://doi.org/10.1091/mbc.E21-03-0107</a> </p><p class="p2" style="margin-bottom:0px;font-feature-settings:normal;font-stretch:normal;font-size:11px;line-height:normal;font-family:helvetica;color:#000000;min-height:13px;"><br class="ms-rteThemeBackColor-1-0"></p><p>Ghosh, A., <b>Fowler, V.M.</b>, 2021. Tropomodulins. <i>Curr. Biol.</i> 31, R501–R503.<a href="https://doi.org/10.1016/j.cub.2021.01.055"> https://doi.org/10.1016/j.cub.2021.01.055</a> </p><p class="p2" style="margin-bottom:0px;font-feature-settings:normal;font-stretch:normal;font-size:11px;line-height:normal;font-family:helvetica;color:#000000;min-height:13px;"><br class="ms-rteThemeBackColor-1-0"></p><p>Alimohamadi, H., Smith, A.S., Nowak, R.B., <b>Fowler, V.M.</b>, Rangamani, P., 2020. Non-uniform distribution of myosin-mediated forces governs red blood cell membrane curvature through tension modulation. <i>PLoS Comput. Biol. </i>16, e1007890.<a href="https://doi.org/10.1371/journal.pcbi.1007890"> https://doi.org/10.1371/journal.pcbi.1007890</a> </p><p class="p3" style="margin-bottom:0px;font-feature-settings:normal;font-stretch:normal;font-size:11px;line-height:normal;font-family:helvetica;color:#0000ff;min-height:13px;"><br class="ms-rteThemeBackColor-1-0"></p><p>Pal, K., Nowak R., Billington N., Liu R., Ghosh A., Sellers J.R., <b>Fowler, V.M.</b>, 2020. Megakaryocyte migration defects due to nonmuscle myosin IIA mutations underlie thrombocytopenia in MYH9-related disease. <i>Blood</i> 135(21):1887-1898. https://doi: 10.1182/blood.2019003064 </p><p class="p2" style="margin-bottom:0px;font-feature-settings:normal;font-stretch:normal;font-size:11px;line-height:normal;font-family:helvetica;color:#000000;min-height:13px;"><span class="Apple-converted-space ms-rteThemeBackColor-1-0"> </span></p><p>Cheng, C., Parreno, J., Nowak, R.B., Biswas, S.K., Wang, K., Hoshino, M., Uesugi, K., Yagi, N., Moncaster, J.A., Lo, W.-K., Pierscionek, B., <b>Fowler, V.M.</b>, 2019. Age-related changes in eye lens biomechanics, morphology, refractive index and transparency. <i>Aging</i> (Albany NY) 11, 12497–12531.<a href="https://doi.org/10.18632/aging.102584"> https://doi.org/10.18632/aging.102584</a> </p><p>Cheng, C., Nowak, R.B., Amadeo, M.B., Biswas, S.K., Lo, W.-K., <b>Fowler, V.M.</b>, 2018. Tropomyosin 3.5 protects the F-actin networks required for tissue biomechanical properties. <i>J. Cell Sci.</i> 131, jcs222042.<a href="https://doi.org/10.1242/jcs.222042"> https://doi.org/10.1242/jcs.222042</a> <br></p><p class="p2" style="margin-bottom:0px;font-feature-settings:normal;font-stretch:normal;font-size:11px;line-height:normal;font-family:helvetica;color:#000000;min-height:13px;"><br class="ms-rteThemeBackColor-1-0"></p><p>Parreno, J., Cheng, C., Nowak, R.B., <b>Fowler, V.M.,</b> 2018. The effects of mechanical strain on mouse eye lens capsule and cellular microstructure. <i>Mol. Biol. Cell </i>29, 1963–1974.<a href="https://doi.org/10.1091/mbc.E18-01-0035"> https://doi.org/10.1091/mbc.E18-01-0035</a> <br></p><p>Parreno, J., <b>Fowler, V.M.</b>, 2018. Multifunctional roles of tropomodulin-3 in regulating actin dynamics. <i>Biophys</i>. Rev. 10, 1605–1615.<a href="https://doi.org/10.1007/s12551-018-0481-9"> https://doi.org/10.1007/s12551-018-0481-9</a> <br></p><p class="p2" style="margin-bottom:0px;font-feature-settings:normal;font-stretch:normal;font-size:11px;line-height:normal;font-family:helvetica;color:#000000;min-height:13px;"><br class="ms-rteThemeBackColor-1-0"></p><p>Smith, A.S., Nowak, R.B., Zhou, S., Giannetto, M., Gokhin, D.S., Papoin, J., Ghiran, I.C., Blanc, L., Wan, J., <b>Fowler, V.M.</b>, 2018. Myosin IIA interacts with the spectrin-actin membrane skeleton to control red blood cell membrane curvature and deformability. <i>Proc. Natl. Acad. Sci.</i> U.S.A. 115.<a href="https://doi.org/10.1073/pnas.1718285115"> https://doi.org/10.1073/pnas.1718285115</a><br></p> | <h2>Professional Experience</h2>
<p>1980-1982 Jane Coffin Childs Postdoctoral Fellow NIADDK, NIH, and Dept Cell Biology and Anatomy, Johns Hopkins University School of Medicine
</p><p>1983-1984 Research Associate, Dept Cell Biology and Anatomy, Johns Hopkins University School of Medicine
</p><p>1984-1987 Assistant Professor, Dept Anatomy and Cell Biology, Harvard Medical School
</p><p>1987-1993 Assistant Professor, Depts Molecular and Cell Biology, The Scripps Research Institute (TSRI)
</p><p>1993-2000 Associate Professor, Dept Cell Biology, TSRI
</p><p>2000-2015 Professor, Dept Cell and Molecular Biology, TSRI
</p><p>2013-pres. Associate Dean for Graduate Studies, TSRI
</p><p>2014-2015 Chair (Acting), Department of Cell and Molecular Biology, TSRI
</p><p>2016-2018 Professor, Department of Molecular Medicine, TSRI. </p>
<h2>Awards & Professional Activities<br></h2>
<p>1973 Phi Beta Kappa (Oberlin College)<br></p><p>1975-1978 National Science Foundation Predoctoral Fellowship Award
</p><p>1980-1982 Jane Coffin Childs Foundation Postdoctoral Fellowship Award
</p><p>1983-1984 NIH New Investigator Research Grant Award
</p><p>1990-1995 American Heart Association Established Investigator Award
</p><p>2001-2003 Chair, Cell and Developmental Function 6 (CDF6) Study Section for Postdoctoral Fellowships and AREA grants, NIH
</p><p>2003 Chair, “Motile and Contractile Systems” Gordon Research Conference, Colby-Sawyer College, NH
</p><p>2009-2013 Erythrocyte and Leukocyte Biology (ELB) and Molecular and Cellular Hematology (MCH) NIH Study Sections<br></p><p>2010 Program Committee for 2011 Annual Meeting, American Society for Cell Biology<br></p><p>2011 Chair, “Red Cells” Gordon Research Conference, Proctor Academy, Andover, NH<br></p><p>2011 Lens and Cataract Program Planning Panel, National Eye Institute, NIH
</p><p>2011-2017 Associate Program Director & Imaging Core Director, San Diego Skeletal Muscle Research Center for NIAMS/NIH P30 Core
</p><p>2013-2015 Scientific Advisory Board, French National Grant, “Le Globule Rouge”, Laboratoires d’Excellence” (GR-Ex), Paris, France
</p>2013-2019<span class="Apple-converted-space"> </span>Associate Editor, Journal of Biological Chemistry<div><br></div><div>2014 Program Co-Chair, Lens Section, International Society for Eye Research XX1st Biennial Conference. 2005- Editorial Board, Cytoskeleton</div><div><br></div><div><p>2012-2018 Editorial Board Member, Journal of Biological Chemistry</p><div>2017 Chair, Lens Section, ARVO Annual Meeting Program Committee<br></div><div><br></div><div>2021-pres. Associate Director, Delaware Center for Musculoskeletal Research, NIH/NIGMS P20 Center of Biomedical Research Excellence (COBRE)</div><div><br></div><div>2023 Elected Fellow of the American Society of Cell Biology<br><br></div></div> | <p>https://fowler.bio.udel.edu/<br></p> | <img alt="Velia Fowler" src="/content-sub-site/PublishingImages/people/vfowler/Fowler_Velia-111319-021,%20crop%203.21.21.jpg" style="BORDER:0px solid;" /> | |
