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The Patrie Laboratory.
Our lab is elucidating the roles that post-translational modifications (PTMs) (e.g., methylation, phosphorylation, acetylation and glycosylation) play in the pathogenesis of immunologic-based diseases, cardiovascular diseases, and cancer. To support the work on rationalizing PTM dynamics and function, graduate and post-doctoral fellows in our lab transcend research boundaries in chemistry, biochemistry and medicine and are exposed to a variety of molecular biology and biochemical techniques, as well as, state-of-the-art proteomics methods (e.g., shot-gun proteomics, imaging mass spectrometry, top-down mass spectrometry and protein biochips).
Examples of Physical Science research in the lab includes:
1) Development of novel mass spectrometry instrumentation.
2) Development of advanced intact protein separation platforms for liquid chromatography mass spectrometry (LCMS).
3) Development of novel imaging mass spectrometry tools that combine protein biochip and immunosensor assays with mass spectrometry. These tools are meant to translate PTM-based biomarkers into clinical diagnostics assays.
4) Development of software/informatics tools to study proteome-wide PTM dynamics
Examples of the diseased based research in our lab includes:
Autoimmune/Neurodegenerative mechanisms in Multiple Sclerosis:
1) A major focus of the laboratory is characterizing the PTMs linked to the disease multiple sclerosis (MS). Studies of the human disease and the murine model, experimental autoimmune encephalomyelitis (EAE), are determining how PTMs on neuronal myelin, the insulating material that surrounds the axons of neurons, serve as molecular bar-codes that regulate healthy and dysfunctional immune response.
2) The characterization of autoantigens targeted by B cells that exhibit a somatic hypermutation pattern that is unique to multiple sclerosis patients.
3) We are characterizing the antigens presented on MHC complexes of T cells that derive from EAE models.
4) We are also interested in understanding the cascade of enzymatic events that promote remyelination during lesion healing.
5) Using our novel imaging mass spectrometry assays with protein biochips we are developing new diagnostic screening tools that exploit PTM-based biomarkers from the cerebrospinal fluid of MS patients.
To support this work our lab collaborates with Drs. Nancy Monson and Nitin Karandikar in the UT Southwestern Multiple Sclerosis Center which provides CSF, tissue, and blood samples from patients characterized by MS subtype (i.e., progressive-relapsing, primary progressive, secondary progressive, or relapsing remitting) and a variety of other demographics, including drug treatments. The Multiple Sclerosis Center evaluates 4500 patients a year and is creating one of the largest biorepositories available containing detailed clinical, radiographic, and paraclinical data (CSF findings, optical coherence tomography findings, and functional scores) and a variety of biologic specimens (including serum, DNA, RNA and peripheral blood mononuclear cells) for each patient.
1) We are also studying PTM function in heart disease. For example, we are exploring how kinase/phosphatase enzymes are driven via circadian regulatory mechanisms.
2) We are exploring the role PTMs play in autophagy and cell death.
3) We are characterizing diverse modifications associated with contractile mechanisms in the heart.
4) Using our novel imaging mass spectrometry assays we are characterizing PTM-based biomarkers from the serum of over ~3000 patients that are part of the Dallas Heart Study.
To support this work we collaborate with a variety of investigators in the Departments of Cardiology and Physiology here at UTSW. This includes the laboratories of Drs. Joseph Hill, Beverly Rothermel and James Stull. The Dallas Heart Study at UT Southwestern is a multiethnic, population-based study intended for unbiased population estimates of biologic and social variables that pinpoint ethnic differences in cardiovascular health. Along with collection of blood samples, patients in the study are subjected to a variety of imaging experiments, including genetics screens, cardiac magnetic resonance imaging and electron beam computed tomography.
1) We are interested in epigenetics (i.e., PTM encoded regulation of chromatin/histone dynamics in gene transcription) and specifically characterizing histone modifications and gene variants that vary across cancerous cell populations.
A fellow’s research experience in the Patrie Lab:
While studying the dynamics of PTMs in various diseases students will be able to train on (or develop) the most advanced proteomics technologies available. This offers students an unparallel experience to probe disease mechanisms at system’s wide level and not just single proteins alone. We take pride in that researchers in our lab are multi-disciplinary coming from diverse backgrounds including molecular biology, medicine, chemistry, engineering, and computer science. We also take pride in that the projects we are pursuing not only promote basic understanding of disease pathology but also have great potential in translating novel findings to the patient bedside.