Faculty and Research
The members of the biochemistry faculty comprise an ideal blend of biochemists, biophysicists, and chemists who collaborate to identify and improve bioactive molecules for such purposes as fighting cancer, Alzheimer’s disease, and other neurodegenerative disorders.
The faculty includes one Nobel Laureate, three members of the National Academy of Sciences, two Howard Hughes Medical Institute Investigators, and one member of the Institute of Medicine.
The Department’s annual retreat in New Braunfels, Texas, provides a relaxing atmosphere for members to keep up with each others’ work.
Though iron and oxygen are required for essential biological processes, their excess can result in oxidative stress. The Bruick Lab has identified mammalian “sensors” of iron and oxygen availability that modulate the stability of key regulatory factors to maintain iron and oxygen homeostasis. We use these findings to validate the therapeutic potential of small molecule antagonists in settings such as cancer.
The Chen Lab studies the synthesis and design of medically important small molecules. We develop new methods and strategies for natural-product synthesis, and design small molecules that modulate cellular functions. We seek to advance the technologies for small-molecule synthesis and develop new drugs for treating cancer and immune diseases.
The Chuang Lab focuses on structure, function, and regulation of mitochondrial protein machines and their clinical ramifications. We currently use structure-based design to develop a new generation of small-molecule inhibitors specific for mitochondrial pyruvate dehydrogenase kinases (PDKs) and branched-chain α-ketoacid dehydrogenase kinase (BDK). These kinase inhibitors have shown good promise in promoting oxidataion of glucose and of branched-chain amino acids, while reducing lipogenesis in animal models for obesity and type 2 diabetes.
The De Brabander Lab focuses on the synthesis of complex molecular architectures. Synthetic targets include both designed and naturally occurring substances with novel structural features and interesting biological function. We also develop novel methodology toward functionality found in complex natural products. We integrate our synthetic program with molecular pharmacology, biochemistry, and cancer biology. Our group also collaborates to discover novel small-molecule activators of programmed cell death, glucagon suppressors for the treatment of diabetes, antitumor agents that selectively target tumor-derived neuronal stem cells and colon cancers with APC truncations, anti-trypanosomal agents for the treatment of African Sleeping Disease, and V-ATPase inhibitors and their role in cancer and as anti-viral agents.
The main theme of our research is the application of synthetic and bioorganic chemistry to problems of biochemical and medicinal relevance. Several of our projects involve collaborations with laboratories specializing in pharmacology, physiology, internal medicine, nephrology, and oncology at UT Southwestern and other institutions.
The Gilles-Gonzalez Lab focuses on understanding the mechanisms by which living organisms respond to oxygen and other physiological gases. Since demonstrating that FixL is a histidine protein kinase that is switched on and off by a sensory heme, we have established that FixL belongs to a much broader family of sensors with varying heme-binding folds and enzymatic activities. Members of this family include diguanylate cyclases, c-di-GMP phosphodiesterases, and transcription factors. Our recent work on the Mycobacterium tuberculosis oxygen sensors DevS and DosT has led us to propose that they control this bacterium’s dormancy, which afflicts about two-thirds of the world’s population. Simultaneously, our studies of Escherichia coli sensors have led us to propose that an O2-regulated complex in this bacterium, which includes diguanylate cyclase DosC and cyclic-di-GMP phosphodiesterase DosP, is a dedicated RNA-degrading machine.
The Hammer Lab uses genetically engineered mouse models to investigate the mechanisms by which liver homeostasis is regulated in the face of hepatic injury or pertubations in hepatic cell fate. One area of investigation addresses the role of p53 in sub-lethal hepatic failure using mice that either lack hepatic expression of ribosomal protein S6 (rpS6) or express a dominantly active form of p53. A second area revolves around the mechanisms by which constitutive activation of wnt/b-catenin and notch.
The Kohler group develops chemical biology methods targeted toward study of glycosylated molecules. Using a metabolically incorporated photocrosslinking analog of sialic acid, we investigate functions of sialylated host molecules in bacteria infection. We also study the role of glycosylation in nucleocytoplasmic transport, making use of a photocrosslinking analog of the O-GlcNAc modification.
The Kürti Lab explores several fundamentally new strategies for the transition-metal-free direct: (i) arylation of arenes; (ii); a-arylation of carbonyl compounds; (iii) primary amination of arylboronic acids and (iv) intramolecular C(sp2)-H amination of arenes. We have also discovered the Rh-catalyzed direct N-H/N-alkyl aziridination of olefins.
The Liu Lab combines classical biochemistry and genetic screening to identify novel factors (e.g. Dicer, R2D2, C3PO, and others) and characterize their precise roles in the RNA interference and microRNAs pathways. We have recently ventured into sleep research, and hope to decode this fundamental mystery by combining forward genetic screening, classical biochemistry, and chemical biology.
The MacMillan Lab uses marine-derived bacteria to search for biologically active natural products useful as antibiotics and anticancer agents. We use a combination of microbiology, chemistry, and cell biology to understand the role natural products can play in human health.
The McKnight Lab divides its efforts and interests between studies of P7C3, a neuroprotective chemical, and studies of intrinsically disordered “low complexity” (LC) sequences associated with DNA and RNA regulatory proteins. We hypothesize that these LC sequences reversibly polymerize in a manner that facilitates sub-cellular organization. The later ideas point toward a “solid-state” conceptualization of information transfer from gene to message to protein.
Research in the Mendelson Laboratory focuses on genetic and epigenetic regulation of surfactant protein-A gene expression in fetal lung, transcriptional regulation of aromatase (CYP19) gene expression in estrogen-producing tissues and in breast cancer, and mechanisms in the initiation of term and pre-term labor. Our research has great relevance to human disease.
The Mirzaei Lab focuses on two main areas of research: target ID and biomarker discovery using the power of mass spectrometry based proteomics. One of our primary goals is defining the cancer ubiquitinome to find new targets for drug development and biomarker discovery. Defining the HeLa proteome is another ongoing effort, to provide maximum coverage and number of targets for biomarker validations.
The High Throughput Screening Core Facility focuses on the discovery and pre-clinical development of new small-molecule therapeutics. The core also supports identification and characterization of novel biological targets and pathways for therapeutic intervention in cancer, neuro-degeneration, metabolic diseases, parasitic infections, and other disease states.
The Ready Group focuses on chemical synthesis, including medicinal chemistry, natural products synthesis, and development of methodology. We are broadly interested in the synthesis of biologically active small molecules, especially complex anti-cancer agents, from marine and bacterial sources and of synthetic compounds discovered through unbiased high-throughput screening.
The Roth Lab focuses on discovering drug-like small molecules with interesting biological properties and then determining the mechanisms by which they act. With chemists and pharmacologists at UT Southwestern, we improve the potency and other properties of these chemicals so they become useful leads for developing therapeutic drugs.
The Tambar Group develops new strategies and concepts in synthetic chemistry to address challenging biomedical problems. Our chemical discoveries will be applied to the synthesis of natural biologically active products and their unnatural analogs. We are also taking advantage of unique opportunities in medicinal chemistry at UTSW.
The Tu Lab investigates how metabolism coordinates with fundamental cellular processes such as cell growth, cell division, autophagy, and mitochondria biogenesis. We use budding yeast as a model system and explore related regulatory mechanisms in mammalian cells.
The Uyeda Lab focuses on biochemical mechanisms by which the transcription factor carbohydrate response element binding protein (ChREBP) converts excess dietary carbohydrate to fat. Our current goals are to determine the glucose signaling mechanisms, and roles played by ChREBP in the brain.
The Williams Lab optimizes small-molecule leads as in vivo tool compounds and therapeutics. We evaluate drug metabolism, solubility, protein binding, and pharmacokinetics. We work closely with chemists to alter these characteristics for optimal activity in vivo. Our primary analytical tool is LC-MS/MS.
The Yu Lab develops novel mass spectrometry technologies (instrumentational and computational) and uses them to address fundamental questions in cancer biology. The processes that transform a normal cell into a cancerous one are often manifested at the protein level. We employ cutting-edge proteomics tools to characterize the cancer-signal transduction networks and to elucidate the molecular mechanisms of tumorigenesis.