ECHI-night

ECDOI 4th Floor

Tell a friend about this page.
All fields required.
Can be sent to only one email address at a time.
Share Facebook Icon Twitter Icon

4TH FLOOR

cabot lab - website

The Cabot Lab
(7/9/14)The Cabot Lab focuses on sphingolipid metabolism as it relates to cancer growth and therapy. Sphingolipid metabolism is an area of cancer research that has risen to clinical prominence over the last 15 years. This is because ceramide, the aliphatic backbone of sphingolipids, acts as a powerful tumor suppressor, whereas its glycosylated product, glucosylceramide, catalyzed by the enzyme glucosylceramide synthase, is anti-apoptotic and a biomarker of multidrug resistance, as identified by Cabot in the mid-1990's. Acid ceramidase, another important sphingolipid enzyme regulator of cancer cell growth, has recently been identified as candidate gene for development of new cancer diagnostics and touted as a therapeutic target in metastatic cancer. Like glucosylceramide synthase, acid ceramidase dampens the tumor suppressor properties of ceramide via ceramide hydrolysis and leads to the generation of sphingosine 1-phosphate, a powerful cancer cell mitogen. Thus, sphingolipid metabolism is a dynamic process with complex orchestration, impact, and clinical applications. Importantly, these enzymes are druggable targets.

The Choe Lab

The Choe Lab
The Choe Lab is working on the structure and function of carbohydrate-related proteins and their application to medical and biotechnological fields through drug discovery and protein engineering. Our biological systems include glucose transporters (important membrane proteins involved in cancer, diabetes and other metabolic diseases), and enzymes and transporters responsible for glucose conjugation and transport of salicylic acid (with role in plant defense against pathogens). We use molecular biology, cell culturing in different systems (bacteria, yeast, insect and human cells), biochemical and biophysical techniques for protein purification and characterization, x-ray protein crystallography, small angle x-ray scattering and computational modeling.

The Ellis Lab

The Ellis Lab
The Ellis uses biochemical, metabolic flux, molecular biology, and genetically manipulated mouse model approaches to understand the regulation and importance of cellular fatty acid metabolism. We are interested in applying this knowledge to find new ways to understand and treat diseases. Our lab has two main research focuses: One focus is on the enzymatic regulation of cellular lipid metabolism within the brain and how this metabolism influences neurological function and susceptibility to neurodegenerative diseases. Specifically, we have identified that an enzyme, acyl-CoA synthetase 6 (Acsl6) is critical for enriching the brain with the neuroprotective omega-3 fatty acid, docosahexaenoic acid (DHA) and are using a murine genetic model to determine the regulation and consequences of Acsl6-mediated fatty acid metabolism. The lab’s second area of research focuses on mitochondrial metabolism in the muscle in relation to cardiac hypertrophy, muscle function, energetic homeostasis, obesity, and diabetes. Specifically, we have determined that muscle fatty acid oxidation is critical for maintaining cardiac and skeletal muscle structure, function, and physiological response to stress, such as diet-induced obesity and insulin resistance, and we continue to investigate the mechanisms therein. Our team of undergraduate, graduate, and postdoctoral researchers are paving the path as the next generation of scientists.

Kelsey Fisher-Wellman

The Fisher-Wellman Lab
The diverse chemical reactivity of sulfur allows for the cysteine thiol moiety to adopt numerous oxidation states (e.g., sulfhydryl; R-SH, disulfide; R-S-S-R, sulfenic acid; R-SOH, sulfinic acid; R-SO2H, sulfonic acid; R-SO3H) throughout the proteome. As such, cysteine thiols in vivo are susceptible to an array of post-translational redox modifications upon reaction with various reactive oxygen, nitrogen and sulfur species (RONS). The majority of these PTMs are reversible owing to the robust capabilities of the glutathione and thioredoxin redox buffering networks, which under normal conditions maintain the cysteine proteome in a ~90% reduced state (i.e., sulfhydryl state).Dynamic fluctuations in the cysteine PTM landscape (i.e., the "redox code") resulting from acute increases in oxidative input (i.e., increased RONS) have been shown to confer control to various cellular metabolic pathways. Such redox signaling mechanisms are believed to have allowed for increasing organismal complexity throughout evolution and as such the integrity of these networks are critical to mammalian fitness. Not surprisingly, loss of redox homeostasis (i.e, decreased "reductive tone") in response to repeated stress has been implicated as a principle driver of various human diseases and the aging process. The central focus of the lab is geared towards deciphering the redox code and identifying the specific control points which break down in response to stress and drive disease. To address this, we will interrogate a variety of research models (e.g., rodents, cell in culture, human subjects) using a combination of highly sophisticated biochemical functional assay platforms combined with large scale analysis of the proteome using state-of-the art mass spectrometry.

geyer lab - website

The Geyer Lab
(7/1/14)The Geyer lab is interested in how retinoic acid (RA) directs the initial steps of male germ cell development. RA regulates the sex-specific timing of meiotic initiation in mice, which in males occurs at postnatal day (P)10. However, RA signaling initiates 1 week prior, at P3-4, yet we know almost nothing about the pathways or mechanisms initiated by RA signaling and their relationship to neonatal male germ cell differentiation. We recently discovered that RA directs neonatal germ cell proliferation, ultrastructure maturation (mitochondria and Golgi biogenesis), modified timing of meiotic initiation, and the expression of differentiation markers such as STRA8 and KIT. In addition, we found that RA stimulates translation of a panel of mRNAs in differentiating spermatogonia, and this discovery is the current focus of investigations in the Geyer laboratory. We are currently using in vivo and ex vivo approaches with neonatal testis explants in combination with RA and a variety of inhibitors to understand how RA signaling enhances the translation of mRNAs encoding critical differentiation markers such as STRA8 and KIT. The identification of pathways activated by RA will provide a significant advance in our understanding of how cell fate decisions are made at the initiation of spermatogenesis and provide insight into the etiology of testicular cancers and male infertility.

houmard lab - website

The Houmard Lab
(7/30/14)The Houmard Lab's primary focus is examining how skeletal muscle metabolism is altered with conditions such as obesity, type 2 diabetes and the aging process, and how a physically active lifestyle can counteract decrements associated with these conditions. Current ongoing projects involve how fat oxidation is altered with obesity, the role of exosomes in the insulin resistance of obesity, the metabolic changes seen with gastric bypass surgery, and how exercise training can rescue the reduction in fat oxidation and insulin resistance seen with obesity.

Huang Lab website

The Huang Lab
(9/08/14)The Huang Lab is currently focusing on answering the following scientific questions: 1)whether exercise induces hypothalamic neurogenesis and 2) which particular neurons in the hypothalamus controls moving behavior. Their plan is to open a new research avenue combining the various neuroscience techniques used on transgenic animal models to determine whole body metabolism with exercise and /or nutrition intervention.

mcclung lab - website

The McClung Lab
(7/25/14)The McClung Lab is focused on understanding the molecular mechanisms of angiogenesis and vascular remodeling in both physiologic and pathologic processes, including: exercise, peripheral artery disease (PAD), atherosclerosis, cardiac and cerebral ischemia, diabetes, and cancer. The lab is interested in how genetic variation may direct the integration of individual cellular responses to ischemic insult, resulting in differential manifestations of tissue pathology in both pre-clinical models and in clinical patient populations. On a deeper level, the lab is studying how single nucleotide polymorphisms affect autophagy, mitochondria, oxidative stress, and signal transduction by endothelial receptor tyrosine kinase (RTKs) in different cell types (skeletal muscle, endothelial, progenitor, smooth muscle, fibroblast). Therapeutic strategies targeting the vasculature in cardiovascular disease have met with little success, and those aimed at preventing tumor angiogenesis result in significant side effects that often result in forced cessation of therapy. The McClung lab hopes to lay the foundation for the development of novel diagnostic and therapeutic tools for tissue ischemia and aid in the refinement of current anti-angiogenic therapies for cancer. The lab currently consists of Dr. McClung (PI), Cameron Schmidt (Graduate Student). Tom Green (currently in Oncology as a Research Associate) will be joining the lab August 1.

neufer lab - website

(9/12/14)The Neufer Lab centers around mitochondria. Their research is directed at deciphering the molecular mechanisms governing mitochondrial bioenergetics and function in the context of the etiology of metabolic disease as well as disease prevention/treatment.

Spangenburg lab

The Spangenburg Lab
(9/30/16) The Spangenburg Lab is focused on elucidating novel mechanisms that regulate physiological and metabolic function of skeletal muscle. The lab employs an integrative experimental approach, in which we use cell culture and animal models to define mechanisms that we then work to translate to the human. Specifically, we have developed skeletal muscle specific-inducible knock out mice and the ability to ablate gene expression in cultured human myotubes through shRNA delivered via AV virus approach. This integrative approach allows us to examine the same loss-of function approach using in vivo animal models and cultured myotubes from humans. The lab has the ability to assess skeletal muscle function on multiple levels including ex vivo muscle force generation, isolated single muscle cells, rotorod, etc. We are able to provide a comprehensive phenotype of the skeletal muscle from a single cell level to the whole muscle level. The lab also employs a number of approaches to assess mitochondrial function including Oroboros based approaches using muscle fiber bundles or Seahorse based approaches. Finally, the lab also has significant expertise with fluorescent imaging of single muscle cells and whole muscle using confocal and two-photon based approaches. The lab is located on the fourth floor of the ECDOI and is funded by the NIH and ADA.

Zeczycki Lab - website

The Zeczycki Lab
(8/05/14)The Zeczycki Lab's focuses on determining the mechanisms of catalysis and unraveling the complexities of allosteric regulation of those multifunctional enzymes that are important to the pathogenesis of disease states. Understanding the activity and regulation of these enzymes is critical for the development of effective therapeutics which can modulate, rather than inhibit, enzyme activity. The current focus of research in our lab is directed towards two different enzymes, pyruvate carboxylase (PC) and transglutaminase 2 (TG2). The aberrant activities of these enzymes are partially responsible for the pathogenesis and exacerbation of Type 2 diabetes and neurodegenerative diseases, respectively. In order to determine the physiologically relevant kinetic, chemical and allosteric mechanisms inherent to these enzymes, our lab uses a combination of in vitro techniques to examine the unique enzymatic biochemical transformations, dynamic domain motions and inter-subunit communication pathways. These techniques, common to the fields of molecular biology, chemical biology and enzymology, include protein engineering, site-directed mutagenesis, steady-state and pre-steady-state kinetics and 1D/2D NMR.