A sample of the SMART Program Project Descriptions are listed below in alphabetical order by last name. Projects may vary and are subject to change. An expanded and updated list of the SMART Program mentors and projects will be available at a later date.

Baker, Mathew - Structure and function of nanomachines. At the NCMI, we employ electron cryo-microscopy and computational biology to visualize and model the complex structures of biological nanomachines. The student will be involved in several aspects of structure determination and analysis of a variety of specimens, from small protein complexes to whole cells. Additionally, there is an opportunity for the student to learn novel protein structure modeling techniques and develop software for the 3D visualization and analysis of these complexes.

Bates, David - Molecular mechanisms of chromosome cohesion in E. coli. We recently showed that after DNA replication, sister chromosomes are physically joined along homologous sequences, analogous to chromosome cohesion in eukaryotes. Interested students will examine two candidate genes for their role in establishing and maintaining chromosome cohesion using a novel cohesion assay, and will map the binding pattern of candidate proteins to the chromosome by chromatin immunoprecipitation and array comparative genome hybridization (ChIP-chip).

Beeton, Christine - Ion channels in the immune system; targets for the treatment of inflammatory diseases. We investigate the phenotype and functions of ion channels expressed on cells involved in inflammatory diseases such as asthma and rheumatoid arthritis with the goal of developing new treatments for these diseases. Our projects combine techniques in cell biology, electrophysiology, and biochemistry and we use both samples from patients and animal models.

Boriek, Aladin - Remodeling of the respiratory pump in COPD, muscle mechanics, computational mechanics of the respiratory system, rib cage mechanics, mechanotransduction of the diaphragm, membrane mechanics, finite element modeling, quantitative analysis of membrane shape, CT imaging analysis.

Botas, Juan - Identification of potential therapeutic targets of neurodegenerative disorders (Ataxias, Huntington’s and Alzheimers) using a genetic approach in model systems.

Cevallos, Manuel - Biofilm prevention in Urinary catheters. Biofilm prevention using an active compound from Cranberry. The future directions will be testing different strains of E. Coli, and other bacteria species (pseudomonas, enterococcus) active compound isolation, and evaluate doses-depend/time. Student will have opportunity to participate on this study, as well in related related studies that are performed in the Lab: Bacterial Interference, test modified catheter surface by nanotechnology, bacterial adherence to cells, and if student desires to participate in the process to enrolling and follow up patients in our studies in Translational Research.

Chan, Lawrence - We are seeking students who are interested in working hard and learning new lab techniques in projects related to diabetes and curing diabetes with gene medicine approaches.

Chang, Eric - Using yeast genetics to study localization of Ras GTPase. We plan to use standard yeast genetics to knock out a few genes that may regulate subcellular localization of Ras proteins. The gene knock out experiments will be performed using a PCR based method. Expression and localization of Ras will be examined by Western blots and microscopy, respectively.

Cooney, Austin - Regulation of gene expression in embryonic stem cells.

Cooper, Thomas -Several projects are available. (1) Analysis of gene expression in heart and muscle of a mouse model of myotonic dystrophy (DM). DM is the second most common cause of muscular dystrophy in the US. Quantitative RT-PCR will measure mRNA levels. Mouse handling is not required. (2) Identify alternative splicing regulators required during skeletal muscle differentiation. ShRNA lentiviral vectors have been constructed and a large panel of differentiation-dependent splicing changes will be screened. (3) 2D analysis of post-transcriptional protein changes during skeletal muscle differentiation.

De Biasi, Mariella - Two projects are available: The first one deals with the use of genetic mouse models to determine the brain areas and the receptors involved in alcohol abuse. The second project deals with the characterization of the role of ubiquitin-like proteins in receptor trafficking. We are particularly interested in the role of the proteasome.

Graham, Brett - Genetic Screen for Suppressors of Mitochondrial Mutant Phenotypes in Drosophila Mitochondrial disease is an important cause of brain-muscle dysfunction and results from defects in oxidative phosphorylation and metabolism. The student will participate in a project to perform a genetic screen in the fruit fly designed to identify suppressors of abnormal eye development caused by mitochondrial dysfunction. The student will learn how to handle flies, recognize abnormal phenotypes, and design/execute genetic crosses and analyses.

Hadsell, Darryl - Developmental changes in the mammary transcriptome of the lactating mouse. The student will use select software packages to analyze and summarize micro-array data that have been collected for mammary tissue RNA or the lactating mouse at 6 time-points during the cycle. Some of the genes identified as different will be reanalyzed by quantitative real-time RT-PCR. The student will also be given the opportunity to write up the work in a manuscript.

Hirschi, Karen - Regulation of vascular development and vascular regeneration.

Jacot, Jeffrey - Tissue Engineering of a Biological Septal Patch. Septal heart defects are the most common type of congenital heart defect. Surgical closure with an acellular patch results in an increased likelihood of asynchronous contraction, arrhythmia and fibrillation. Our lab aims to develop a cellular, biofunctional septal patch with mechanical and conductive properties equivalent to native tissue. This student will choose from projects involving the design and testing of biomaterial scaffolds for a septal patch, the evaluation of the electrophysiology and force generation of engineered tissue, or the culture and evaluation of progenitor cells for use in cellular septal patches.

Jankowsky, Joanna - Making new cells in an old brain. Our group is interested in understanding how specialized parts of the adult brain retain the capacity to make new neurons throughout life, and how the production of adultborn neurons is compromised by diseases of aging such as Alzheimer’s dementia. We have show that the long-term survival of newborn neurons in one of these specialized regions is severely reduced in transgenic mice with Alzheimer’s-like lesions in the brains. We are now working to identify precisely when the newborn neurons are most susceptible, and to examine their morphology at this time point so that we might hone in on the cause for increased mortality in this fragile population of aspiring neurons.

Lacorazza, Daniel - Role of a tumor suppressor in immune cell signalings. We study the transcriptional control of hematopoiesis and development of the immune system, particularly on genes that control cellular quiescence in hematopoietic stem cells and naive T cells. We recently identified a tumor suppressor that inhibits T cell proliferation downstream of T-cell receptor signaling. We are currently studying the impact of this negative regulation on immune response, immunological memory, and leukemogenesis.

Lamb, Dolores - 1) Enhancement of Vitamin D Action in Advance Prostate Cancer Through CYP24 Silencing. 2) Improving the Diagnosis of Congenital Genitourinary Defects. 3) Miscoassisted Fertilization and Genetic Defects in Male Infertility. 4) Leptin-Ghrelin Interplay in the Testis.

Li, Yi - Breast Cancer stem cells. Too often breast cancer treatment are ineffective, because of current therapeutics do not target cancer stem cells. We have already isolated breast cancer stem cells from a unique mouse model. A summer student will join our team to further purify and characterize these cancer stem cells, to study their unique molecular network, and to attempt to treat them with approaches including nanotechnology, immunotherapy, and gene therapy.

Lopez-Terrada, Dolores - Biology of pediatric tumors of the liver (hepatoblastoma).

Mardon, Graeme - Genome-wide identification and functional analysis of Drosophila retinal determination genes.

Morrisett, Joel - Visualization and Quantitation of Proteins involved in Development of Atherosclerotic Plaques & Cardiovascular Disease. MRI 2D Images of carotid endarterectomy tissues are acquired then used to construct 3 D models. Tissues are cut into small sections which are stained with labeled antibodies specific for different marker proteins. The location and intensity of label fluorescence is mapped onto the 3D model, allowing comparison of the location of the atherosclerotic plaques and proteins which may mediate plaque formation. Our ultimate goal is to identify and eliminate the culprit proteins causing the disease.

Nguyen, Hoang - Skin epithelial stem cell maintenance and cell fate specification. The student’s project will focus on a few candidate genes that control stem cell fate in the skin. The project will include characterizing the expression pattern of the candidate genes by performing in situ hybridization and immunofluorescence. The student will employ molecular biology to express the genes of interest in expression vectors and use cell culture to test the function of the genes on skin stem cell proliferation and differentiation.

O’Malley, Bert - Hormones in human health and disease. The lab studies the roles and mechanisms of hormone action, particularly in gene regulation. A number of projects are available that are applicable to cancer.

Overbeek, Paul -Lentiviral Gene Therapy. Recombinant lentiviruses provide promising tools for gene therapy for inherited genetic disorders. We use mouse models for human genetic disease. In our initial experiments, we used a lentivirus to achieve efficient and effective germ-line therapy for albinism. The genetic rescue was stable and transmitted thru the germline, providing long term rescue for the genetic disorder. The summer student(s) will design lentiviral vectors to do gene therapy for other inherited disorder that cause ocular, craniofacial, epidermal and/or mental deficiencies.

Pati, Debananda - Mitotic regulation and cancer. My laboratory is performing research in two main areas: 1) investigation of the molecular basis on aneuploidy in breast cancer models, and 2) mitotic regulation of apoptosis in leukemia. We have identified a set of chromosomal segregation proteins that coordinate aneuploidy, cell division, and apoptosis in cancer tissues in an effort to understand the regulatory network that assures accuracy of chromosomal separation in dividing cells. Our research is aimed at elucidation the molecular mechanism of chromosomal instability through analysis of the factors that mediate sister chromatid cohesion and separation during mitosis. We have recently proposed a new handcuff model for the chromosomal cohesion complex, and have also demonstrated that overexpression of Separase, the cohesion protease that cleaves cohesion subunit Rad21 during mitosis, causes aneuploidy and tumorigenesis. The current focus in my lab is 1) the structural and functional analysis of the cohesion complex, 2) regulation of Separase expression and aneuploidy by p53 and steroid hormones, using Separase transgenic mice models 3) designing and screening small molecular inhibitors against Separase enzyme active site and testing efficacy for tumor regression using our recently developed Separase inducible mouse mammary tumor model, and 4) identification and characterization of a novel nuclear protease that cleaves cohesion Rad21 for apoptosis induction.

Patke, Christina - Preclinical Development of the Green Tea Catechin, Epigallocatechin Gallate (EGCG) as an HIV -1 Therapy. Previously, we showed inhibitory effect of EGCG on binding of HIV-1 gp120 to CD4 on T cells. Research on p24 inhibition and cell and immune function have lead to development of a phase 1 clinical trial. The next phase in the research is the development of EGCG as a microbicide in HIV-1 prevention. The research in this field will involve effects of EGCG on mucosal immunology and HIV inhibition via the mucosa. Research methodologies to be involved; dendritic cell isolation and culturing, EIA, ELISA.

Pautler, Robia - The role of GMS gangliosidosis in the development of Alzheimer’s Disease Pathology.

Salazar, Jorge - Brain Protection During Cardiac Surgeries. We use an animal (piglet) model of cardiopulmonary bypass to look at brain protection strategies. In particular, we are investigating oxidative stress and inflammatory responses after different surgical strategies.

Smith, C. Wayne -Inflammatory aspects of obesity. The project involves investigation of the inflammatory aspects of obesity in an animal model, mice fed a defined high fat diet. Within days of beginning a high fat diet, aspects of the innate immune system in adipose tissues become activated and there is progressive infiltration of the fat tissues with leukocytes, increased production of inflammatory cytokines and chemokines, and developing low grade systemic inflammation. The student will participate with the research team working on this project in the investigation of specific leukocyte subsets, inflammatory mediators on anti-inflammatory factors.

Trautner, Barbara - Preventing catheter-association infection. My laboratory studies prevention of catheter-associated urinary tract infection through bacterial interference. We are interested in genetic manipulation of E. coli to create a benign, protective biofilm on urinary catheters that discourages catheter colonization by pathogens. A student involved in this project would set up bacterial adherence experiments on various modified surfaces. The student would also be involved in imaging the adherent organisms using microscopy. The student could participate in cloning various biofilm genes as well as studying gene expression through QRTPCR.

Van den Veyver, Ignatia - Mouse Models of human disease. We identified that PORCN, a gene on the X-chromosome encoding the human homologue of the Drosophila Porcupine protein is mutated in patients with Goltz syndrome or Focal Dermal Hypoplasia (FDH), a rare developmental disorder. FDH is a rare disorder with multiple abnormalities involving primarily skin, bones of fingers and toes, teeth and eyes. Porcn in mouse and Porcupine in Drosophila are endoplasmic reticulum (ER) transmembrane proteins that lipid-modify WNT proteins, which is thought to be essential for their secretion and normal WNT signaling. We are currently generating mouse models with conditional inactivating mutations in Porcn. The student will participate in characterization of the mice. In addition we are studying the effect of various mutation s in cell culture assays, which the student can also participate in. The student will work under supervision of an experience postdoctoral researcher.

Wehrens, Xander - Molecular basis of heart failure. Student will be involved in translational studies into the molecular basis of heart failure and sudden cardiac death. The mentor’s lab has generated several mouse models with genetic mutations in calcium channel-associated proteins, found in patients with heart failure. Student will be involved in studying the effects of abnormal calcium cycling via these proteins on the structure and function of the mouse heart and hear muscle cells, using a variety of techniques (biochemistry, electrophysiology, imaging).