Browsing by Subject "Genomics"
Now showing 1 - 11 of 11
- Results Per Page
- Sort Options
Item The challenge of precision medicine: ethical, legal & clinical issues in genomic medicine (The Daniel W. Foster, M.D., Visiting Lectureship in Medical Ethics)(2015-11-03) Wolf, Susan M.Genomics is advancing at a tremendous rate, bringing powerful new capabilities but also big challenges to clinical practice and research. With the federal government launching the Precision Medicine Initiative, the time to face those challenges is now. Genomic medicine raises fundamental issues including the role of patient choice, the development of quality standards, the privacy of sequence data, return of results and incidental findings, protection of patient privacy, and responsibilities to share information with the family. This lecture will analyze those challenges and suggest a way forward in biomedical research as well as clinical care.Item CRISPR and gene editing: one tool to rule them all(2017-05-09) Wolinetz, Carrie D.Advances in gene editing, particularly the development of CRISPR-cas9, have allowed for new applications of this technology, ranging from gene drives to development of new animal models for research. This emerging biotechnology is pushing the boundaries of science, even as it provides new and evolving challenges to our policy framework and oversight mechanisms. How do we ensure responsible and feasible oversight while not constraining scientific progress that expands our knowledge base and improves human health? What are the intersection points between new gene editing applications and the current policy landscape?Item Donald W. Seldin, M.D., Research Symposium finalist presentations(2021-04-23) Arvind, Ashwini; Elias, Roy; McAdams, Meredith; Salazar, Alonso Pezo; Rao, Shreya; Sheth, RahulThis edition of the UT Southwestern Internal Medicine Grand Rounds features presentations by the six Foster Fellows selected as finalists from the Sixth Annual Donald W. Seldin, M.D. Research Symposium, which was held on April 23, 2021. These Foster Fellows presented work that spanned the breadth and depth of scholarly activity across the department, and at the close of Grand Rounds, one will be selected as the 2021 Seldin Scholar, in honor of Dr. Donald W. Seldin. The Grand Rounds presentation also includes additional awards honoring Clinical Vignettes and an award for work in Quality and Education at Parkland Hospital.Item Evaluating the Clinical and Financial Impact of Multi-Gene Panel Testing(2021-05-01T05:00:00.000Z) Haque, Waqas Zia; Hsiehchen, David; Syed, Samira K.; Kazmi, SyedBACKGROUND: Medical management of advanced cancers is increasingly guided by predictive biomarkers. Tumor mutation testing using commercial assays examining select gene panels is now incorporated in the standard work-up of advanced cancers. With some exceptions, existing and emerging biomarkers remain inadequate clinical tools for many patients, and anecdotal evidence and small phase trials have driven much of the enthusiasm for biomarker-driven treatments. The purpose of this study is to assess predictive clinical factors of successful gene mutation testing and to determine whether tumor mutation testing directly impacts clinical practice. METHODS: All submitted test requests from UT Southwestern faculty to Foundation One were abstracted for test success and mutation results. Patients were cross-referenced in the EPIC electronic health record information. To evaluate practice changes and patient outcomes after one-year of follow-up, we collected data from the first 100 patients that underwent next generation sequencing testing (excluding PD-L1 testing) in 2020. RESULTS: Among the 100 patients studied, the typical patient was close to older age (mean age 58.7 years), female (56%), Caucasian (52%), insured (71%), and with stage 3 or 4 cancer (79%). The most common tumor types were breast (20%), colorectal (18%), and myelodysplastic syndrome (9%). 20% of patients (20/100) were found to have an actionable mutation and 2 patients were enrolled in clinical trials due to Foundation Medicine testing. Among the 20 patients with an actionable mutation, 5 of them (25%) had a change in therapy. All of these patients responded to the change in therapy with stable disease, and while three of them started the therapy within a month of the Foundation testing resulting, the other two waited 5 and 11 months. The fifth patient was actually found to not have disease but was placed on a maintenance therapy as a result of the testing. CONCLUSIONS: While precision medicine offers the promise of better understanding genomic drivers of disease, it is unclear if the benefits of such an approach outweigh the risk on a population level and if resulting changes in patient care are superior as compared investigator-chosen therapies. Medical oncologists should continue to apply intelligent and judicious use of Foundation Medicine testing.Item Genomic medicine in internal medicine practice(2023-03-24) Gharavi, Ali G.Item Genomics of Butterflies(2021-05-01T05:00:00.000Z) Zhang, Jing; Takahashi, Joseph; Grishin, Nick V.; Hobbs, Helen H.; Borek, DominikaThe success of next generation sequencing technologies enabled us to study biological questions by comparative genomics of a large group of organisms. We developed methods to sequence and comparatively analyze genomes of butterflies and address general questions of molecular evolution and connection between genotype and phenotype. First, we study mimetic convergence and divergence on a phylogenetic group of butterflies revealing many instances of rapid phenotypic changes between close relatives. Second, we sequence and analyze the genome of a gypsy moth, a notorious pest accidentally introduced to American from Europe and hypothesize about the differences in flight capacity of different moth populations. Third, we study speciation in Texas butterflies and uncover general criteria and molecular mechanisms for speciation across central Texas suture zone. Finally, we obtain whole genome shotgun sequences of all 845 butterfly species recorded from the United States and Canada, and learn about the patterns of their speciation and rapid diversification, connecting them to possible molecular mechanisms such as gene exchange through hybridization. As a result, we see that butterflies are a promising group of model organisms to connect molecular and organismal biology by means of genomics, ripe in future discoveries.Item Precision cardiovascular medicine in the post-genomic era(2020-01-03) Munshi, NikhilItem Regulation of Brain-Derived Neurotrophic Factor in the Adult Mouse Brain(2005-08-11) Malkovska, Irena; Parada, Luis F.In the adult central nervous system (CNS) brain-derived neurotrophic factor (BDNF) has been implicated in neuroprotection and synaptic plasticity among other functions. However, relatively little is known of its regulation. In this thesis, we attempted to learn more about BDNF regulation by means of: an in situ hybridization study of the four distinct untranslated exons in the adult mouse brain; use of transgenic animals to define BDNF promoter regions; and use of comparative genomics to identify evolutionarily conserved regions of BDNF. The in situ hybridization study suggests that the four distinct BDNF promoters are differentially regulated and that neighboring promoters are coregulated. Also it appears that all four promoters function in most of the same nuclei of the adult CNS. Inspite of the large size of the transgenic constructs used in this study specific to exons 1/2 and 3/4 (11.4 kb and 16 kb respectively), they were insufficient to mediate endogenous-like BDNF expression in the adult CNS. However, this study suggests that these regions may drive endogenous-like expression in a subset of nuclei (random chance integration cannot however be ruled out). The bioinformatics study revealed 9 highly conserved elements that are good candidates for cis-regulatory elements of BDNF. In conclusion, the regulation of the BDNF gene appears far more complicated than was previously predicted.Item Steroids: how much is too much?(2017-07-14) Quiceno, Guillermo AndresItem Towards Prediction of Phenotype from Genotype(2017-04-14) Cong, Qian; Otwinowski, Zbyszek; Grishin, Nick V.; Hobbs, Helen H.; Deisenhofer, JohannPredicting phenotype from genotype represents the epitome of biological questions. As a multiscale problem, it starts from predicting exons and culminates with modeling of whole organisms. Focusing on the molecular level, I studied the relationship between sequences and protein spatial structures and analyzed proteins with similar sequences but different structures. To aid the assessment of structure prediction, I developed a method to rank the predictions of proteins with new folds, a very challenging problem that was previously addressed by expert inspection. Then, I developed a set of computer programs and scripts to predict various structural and functional properties of proteins from their sequences and implemented them as a public web-server. I applied these methods to important agricultural (citrus disease) and medical (Ebolavirus) problems. Moving on to organismal level predictions, I sequenced, annotated and analyzed complete genomes of butterflies and suggested hypotheses about genetic determinants of their behavior and other phenotypic traits. Taken together, these applications highlight the achievements possible today and challenges that lie ahead.Item Understanding RNA Regulation Through Analysis of CLIP-Seq Data(2015-11-18) Wang, Tao; Mendell, Joshua T.; Xie, Yang; Xiao, Guanghua; Mangelsdorf, David J.; Zhang, Michael Q.The past decades have witnessed a surge of discoveries revealing RNA regulation as a central player in cellular processes. The advent of cross-linking immunoprecipitation coupled with high-throughput sequencing (CLIP-Seq) technology has recently enabled the investigation of genome-wide RNA binding protein-RNA interactions, which is a very important component of RNA-regulation. However, proper and systematic bioinformatics analysis of CLIP-Seq data is still lacking and challenging. For the past few years, I have been devoting my research to methodological developments of CLIP-Seq data analysis, and developed MiClip and dCLIP for peak calling and differential analysis of CLLIP-Seq data, respectively. I have also applied my CLIP-Seq analysis pipelines in on-campus collaborating projects, in which I identified ORF57 and nuclear AGO2 binding sites. Finally, I conducted analysis of public CLIP-Seq datasets to systematically characterize RNA binding protein targeting sites on circular RNAs.