• September-11-NCB-Cover

    Microglia (in green) invade the cerebellum of an adult mouse after bone marrow transplantation and are found in close contact with Purkinje neurons (in red). This treatment in a mouse model of the neurodevelopmental disease Rett syndrome results in arrest of pathology.

    Derecki NC, Cronk JC, Lu Z, Xu E, Abbott SB, Guyenet PG, Kipnis J., Nature. 2012; 484:105-9

    Photo Credit:  Jim Cronk, Kipnis Lab

  • Journal of Cell Science 3-2013 - Bloom3

    Cultured wild-type mouse neurons were incubated for 24 hours with amyloid-β oligomers in the presence of the synthetic nucleotide bromodeoxyuridine (BrdU), followed by immunofluorescence staining using antibodies against microtubule-associated protein (MAP2, green) to identify neurons and against BrdU (red) to identify newly synthesized nuclear DNA.

    Seward ME, Swanson E, Norambuena A, Reimann A, Cochran JN, Li R, Roberson ED, Bloom GS., J Cell Sci. 2013; 126:1278-86

     

  • DeSimone-Dev-Cell-2012-Weber-Final-Cover

    A novel cadherin-dependent mechanosensitive process is responsible for polarized protrusion in collectively migrating cells. Local tugging forces on cadherins at the rear of the cells direct protrusive activity at the front. The mechanism responsible involves a novel mechanosensitive cadherin complex with links to the keratin intermediate filament cytoskeleton.

    Weber GF, Bjerke MA, DeSimone DW., Dev Cell. 2012; 17:22(1):104-15

  • Hui-Li-Cancer-Discovery-cover-July-2012

    Cis-splicing, wherein transcription spans two independent genes, mediates gene fusions in prostate cancer cells.  This results in the generation of new gene product without the need for DNA rearrangement.  This mechanism can result in new drivers of tumor progression.

    Zhang Y, Gong M, Yuan H, Park HG, Frierson HF, Li H., Cancer Discovery. 2012;  2:598-607

  • Kendall cover

    In order to resist clearance with the normal flux of intestinal contents and colonize the gastrointestinal (GI) tract, many enteric pathogens express fimbriae, which are extracellular structures that promote binding to host tissue. We have reported that the biologically relevant molecules ethanolamine and choline, which are abundant in the GI tract, promote the expression of fimbriae in enterohemorrhagic Escherichia coli (EHEC) O157:H7. Visible fimbrial structures are present on the surface of EHEC grown in ethanolamine, which is shown in the cover image.

    Gonyar LA, Kendall MM., Infection and Immunity. 2014; 82: 193-201

What’s New With Our Students?

AWARDS AND FELLOWSHIPS:

 

Bhairav Mehta has received a Predoctoral Fellowship from the Mid-Atlantic Affiliate of the American Heart Association.

Bhairav Mehta 2014 AHA FellowshipThe objective of the fellowship is to help initiate careers in cardiovascular and stroke research by providing research assistance and training. As well the fellowship will provide Bhairav one year of support.

 

Congratulations Bhairav!

June 2014

______________________________________________________________________________________________________

 

Emily Mercadante 2014

 

Exciting news for Emily Mercadante!  Emily has been awarded the NIH National Research Service Award for Predoctoral Fellowships to Promote Diversity in Health-Related Research.  The fellowship is designed to promote diversity among the nation’s scientists and will provide Emily up to three years of support.

Congrats Emily!

June 2014

___________________________________________________________________________________________________

Congratulations to the recipients of the 2014 American Heart Association Fellowship!

 

Samantha Adamson – Pharmacology / Mentor – Norbert Leitinger

Lauren Biwer – Biophysics / Mentor – Brant Isakson

Brittany Durgin – Physiology / Mentor – Jessica Connelly, Gary Owens

Brittany Earnest – Biomedical Engineering / Mentor – Brian Helmke

Sarah Gray – Pharmacology / Mentor – Eugene Barrett

Ryan Haskins – Experimental Pathology / Mentor – Gary Owens

Becky Wilson – Biochemistry /  Mentor – Zhen Yan

 

Samantha Adamson 2014 AHA Lauren Biwer 2014 AHA Brittany Durgin 2014 AHABrittany Earnest 2014 AHASarah Gray 2014 AHARyan Haskins 2014 AHABecky Wilson 2014 AHA

Samantha Adamson, Lauren Biwer, Brittany Durgin, Brittany Earnest, Sarah Gray, Ryan Haskins, Becky Wilson

May 2014

_________________________________________________________________________________________________________________________

Congratulations to UVa BME PhD candidate, Eric Greenwald winner of the the 2014 Wagner Fellowship.

This fellowship is made possible thanks to the wonderful generosity of Dr. Robert R. Wagner M.D. and his wife Mary.

2014 Wagner Fellowship Recipient

Great job Eric!

May 2014

_________________________________________________________________________________________________________________________

Alex Lohman – 2014 Michael J. Peach Outstanding Graduate Student Award Alex Lohman 2014 Hungerford Award

Chelsi Snow – 2014 Jill E. Hungerford Prize in Biomedical Sciences Chelsi Snow 2014 Peach Award

Madison Stellfox 2014 GBS Leadership AwardMadison Stellfox – 2014 GBS Student Leadership Award

 

 

 

 

 

2014 Outstanding Graduate Students Awards

  • Biochemistry and Molecular Genetics -  Chelsi Snow (Dr. Bryce Paschal, Mentor)
  • Biomedical Engineering – Karen Ryall (Dr. Jeff Saucerman, Mentor)
  • Biophysics – Aravinda Kuntimaddi (Dr. John Bushweller, Mentor)
  • Cell and Developmental Biology – Jianyi Lee (Dr. Xiaowei Lu, Mentor)
  • Microbiology, Immunology, & Cancer Biology – Christine Coquery (Dr. Loren Erickson, Mentor)
  • Molecular and Cellular Basis of Disease -  Heather Perry (Dr. Coleen McNamara, Mentor)
  • Neuroscience – Benjamin Thiede (Dr. Jeff Corwin, Mentor)
  • Pharmacology – James Eaton (Dr. Thurl Harris, Mentor)
  • Molecular Physiology & Biological Physics – Alex Lohman (Dr. Brant Isakson, Mentor)

2014 Poster Prize Awards

  • 1st Place – James Cronk & Xinyuan Cui
  • 3rd Place – Emily Moser

April 2014

_________________________________________________________________________________________________________________________

BIMS students, Karen A. Ryall, Brandon M. Kenwood and Kristopher H. Chain, are among authors in a newly published article in the Journal of Biological Chemistry.
http://uvaconnect.com/featurestory/2014/04/03/new-tool-can-check-cells-batteries/

UVA Develops New Tool to Check Cells’ ‘Batteries’

By Illuminating Mitochondria, Researchers Shed Light on Disease, Human Health

CHARLOTTESVILLE, Va., April 3, 2014 – Under the microscope, they glow like streetlights, forming tidy rows that follow the striations of muscle tissue. They are mitochondria, the powerhouses of cells, and researchers at the University of Virginia School of Medicine have created a method to illuminate and understand them in living creatures like never before. Not only can the researchers make the mitochondria fluoresce, to glow for the microscope, but they can discern from that fluorescence the mitochondria’s age, their health, even their stress level. And ultimately that glow, in its soft reds and greens, will shed light on human health and a massive array of illnesses, from diabetes to Parkinson’s disease to cancer.

“Mitochondrial health is important for physiology and disease. That is well known. However, the whole field of mitochondrial health is largely unexplored, in large part because of the lack of useful tools. This has hindered the understanding of the importance of mitochondria in disease development,” said UVA researcher Zhen Yan, PhD, of the UVA Cardiovascular Research Center. “With this study we have, for the first time, shown that we can use a reporter gene to measure mitochondrial health robustly in vivo. We believe this tool will allow us to get into the field of mitochondrial biology like never before.”

“Before, we could see the mitochondria under an electron microscope. That showed us only what they looked like,” Yan said. “Now we can measure the health of millions of mitochondria at the click of a button.”

Health and Stress
Yan and his team based the new tool on a reporter gene, a type of gene used in scientific research to determine the activity and function of other genes. The reporter gene produces a protein that glows green when newly made; the protein then transitions to red as it ages. By giving the reporter gene specific targeting directions, the UVA researchers were able to instruct the protein to enter the mitochondria, setting them aglow. “So now we have fluorescent mitochondria, which are fluorescent green initially and then, as the mitochondria age or become oxidized, they transition to red, so that we can assess the oxidation status,” said Rhianna Laker, PhD, a postdoctoral fellow in Yan’s lab and the lead author of a new paper detailing the work.

The researchers have put their tool to the test in flies, worms and mice. They found that mice fed a high-fat diet had more red mitochondria, meaning the mitochondria were stressed or oxidized, while mice that exercised had more green mitochondria, Laker said. That finding speaks both to the importance of exercise and to the potential diagnostic power of the new tool, dubbed the MitoTimer.

The Big Picture
Taking advantage of the wide-ranging expertise at the School of Medicine, Yan’s lab collaborated with Jeff Saucerman, PhD, of the Department of Biomedical Engineering, to take the work to the next level. Saucerman’s team has developed a computer program that can analyze the degree of mitochondrial fluorescence to assess both individual mitochondria and the overall ratio of red to green in a particular area. That ratio speaks to the health of the cells. “The mitochondria are both the powerhouse of the cell and a sensor of metabolic state and stress,” Yan said.

The findings have been published online in the Journal of Biological Chemistry and will appear in a forthcoming print edition. The article was authored by Rhianna C. Laker, Peng Xu, Karen A. Ryall, Alyson Sujkowski, Brandon M. Kenwood, Kristopher H. Chain, Mei Zhang, Mary A. Royal, Kyle L. Hoehn, Monica Dirscoll, Paul N. Adler, Robert J. Wessells, Jeff Saucerman and Zhen Yan.
____________________________________________________________________________________________________

Lindsey BrintonCongratulations to UVa BIMS Graduate Student, Lindsey Brinton winner of the People’s Choice Award for competing in the international thesis challenge –  Universitas 21 (U21) Three Minute Thesis Online Competition 2013!  Thank you to all who voted!!!

Way to Go Lindsey!!!

 http://www.universitas21.com/article/research/details/227/2013-peoples-choice

__________________________________________________________________________________________________

Christine Coquery, an Immunonolgy Ph.D candidate in the lab of Loren Christine CoqueryErickson has received a Ruth L. Kirschstein National Research Service Award. The Role of B Cell Maturation Antigen in Controlling Tolerance.The establishment of long-lived plasma cells (PC) is a hallmark of the adaptive immune response and is critical for host protection against pathogens. In autoimmune diseases, such as systemic lupus erythematosus (SLE), this process is disrupted to generate self-reactive long-lived PCs (LL-PCs) that produce pathogenic auto-antibodies. This project tests the hypothesis that B Cell Maturation Antigen (BCMA), which is not only present on B lymphocytes but also on T follicular helper (TFH) cells, in the context of an inflammatory environment, that help to drive proliferation and differentiation of PCs, is 1) a critical regulator of TFH cells in autoimmunity and 2) signaling through BCMA on TFH cells can modulate their cytokine production, proliferation, and survival.The overall goal of this project is to define the qualities of TFH cells in autoimmune-prone mice in the presence and absence of BCMA, and to determine their role in the development of long-lived PCs in order to understand the role of BCMA in mediating tolerance.

Previous Education: MS Biomedical Studies, Baylor University; BS Human Biology, University of California San Diego(BIMS 8/2013)


Steven Griffith, a Biochemistry and Molecular Genetics Ph.D. candidate Steven Griffithin the lab of Gary Owens has received a fellowship from the Mid-Atlantic Affiliate of the American Heart Association. The role of H3K4me2 in Smooth Muscle Cell Phenotypic Modulation. A fundamental question in developmental biology is understanding how multipotent embryonic stem cells (ESCs) that share the same DNA sequence can acquire unique characteristics that enable a large variety of functions.  One theory postulates that, while genetically identical, ESCs within the blastocyst are epigenetically distinct and thus are capable of responding rapidly to extracellular and environmental cues that cause differential regulation of gene expression and allow the cells to differentiate into various lineages.  This, in turn, results in the initial cell heterogeneity.  Once this heterogeneous cell population is established, cellular determination is then extended through both intrinsic and extrinsic mechanisms arising from the availability of metabolites, environmental cues, matrix components, cellular location, and morphogens.  These factors gradually program cells down a specific lineage path, resulting in the generation of committed, distinct cell populations and tissues that maintain their specialized characteristics through subsequent cell divisions.  The mechanism through which cells retain this ”lineage memory” is thought to arise through epigenetic changes, including histone modifications, DNA methylation, and ATP-dependent chromatin remodeling.  This project tests the hypothesis that smooth muscle cells (SMCs) undergo reversible phenotypic modulation during vascular repair in vivo and that this process is dependent on an epigenetic lineage memory control process involving stable histone modifications of SMC specific gene loci. My work will definitively determine whether or not Smooth Muscle Cells are capable of undergoing phenotypic modulation in response to vascular injury, a process long suspected to be a major player in a large array of vascular diseases (such as atherosclerosis) as well as determine if removal of a single epigenetic mark at specific gene loci in an individual cell type results in loss of cellular memory in vivo.

Previous Education: BS Biochemistry, Schreiner University - Kerrville, TX(BIMS 8/2013)


Ryan Llewellyn, a Microbiology Ph.D. candidate in the lab of Amy IMG_0311Bouton has received Ruth L. Kirschstein National Research Service Award for Individual Predoctoral Fellows from the National Institutes of Health. The Role of FAK in Regulating Macrophage Migration and Function in Mammary Tumors.  Our research explores the fundamental contribution of Focal Adhesion Kinase (FAK) to macrophage migration and function, which may contribute to regulation of breast tumor progression. Mice with FAK conditionally deleted in myeloid lineage cells (FAKΔmyeloid) were crossed with mice that develop spontaneous breast carcinomas due to expression of the MMTV-PyMT transgene.  FAKΔmyeloid MMTV-PyMT mice showed significantly enhanced primary tumor outgrowth compared to wildtype (WT) littermate MMTV-PyMT animals. Based on data generated from our lab, we hypothesize that monocytes upregulate FAK and differentiation into mature macrophages once they have extravasated out of the tumor vasculature and enter the tumor parenchyma.   This, in turn, could promote increased movement of these cells within the tumor microenvironment, which may help to control tumor size/outgrowth through functions that ultimately mediate anti-tumor effects. To test this hypothesis, we are first determining if FAK expression in macrophages regulates the migration or localization of these cells in the tumor. In parallel, we are assessing whether FAK expression regulates macrophage functionality in the tumor. This research will provide new insights into the mechanisms driving breast tumor growth and identify new considerations for treating breast cancer patients.

Previous Education: B.A. in Biology, University of Virginia(BIMS 8/2013)


What’s New With Our Faculty?

Cellular Microbiology4- volume 15 number 8 aug 2013 Alison K. Criss, Ph.D., Department of Microbiology, Immunology and Cancer Biology

Fluorescence micrograph of primary human neutrophils infected with the bacterium Neisseria gonorrhoeae, showing that some bacteria remain viable intracellularly. Internal viable bacteria appear green, internal nonviable bacteria appear red, external viable bacteria appear turquoise (blue and green), and external nonviable bacteria appear magenta (blue and red). Neutrophil nuclei also fluoresce red. N. gonorrhoeae can survive within neutrophils by residing in immature phagosomes that do not fuse with primary (azurophilic) granules.

Johnson MB, Criss AK., Cell Microbiol. 2013; 15(8):1323-40

 

Egelman-JMB-2011-DinIEdward H. Egelman,  Ph.D., Department of Biochemistry and Molecular Genetics

Two modes of binding of DinI to RecA filament provide  new insights into the regulation of the SOS response by the DinI protein.

 

 

Galkin VE, Britt RL, Bane LB, Yu X, Cox MM, Egelman EH.,  J Mol Biol. 2011; 408(5):815-24

 

 

Minor-Crystal-Growth-Design-coverWladek Minor, Ph. D., Department of Molecular Physiology and Biological Physics

The TetR family transcriptional regulator TM1030 from the hyperthermophile Thermotoga maritima is shown in a complex with DNA. The crystals in the background were grown in temperatures ranging from 4 – 50°C. Crystallization at elevated temperatures is uncommon, even for proteins from mesophilic and thermophilic organisms. The series of structures reported in this manuscript  show that such proteins can be stable at elevated temperatures and that the quality of the crystallographic data and subsequent refined structures do not depend on the crystallization conditions.

Koclega KD, Chruszcz M, Zimmerman MD, Bujacz G, Minor W., Cryst Growth Des. 2009; 10(2):580