Department of Cardiovascular Sciences
The Department of Cardiovascular Sciences at Houston Methodist is recruiting faculty in the following areas.
For more information, contact John P. Cooke, MD, PhD, chair of the Department of Cardiovascular Sciences and Director for the Center for Cardiovascular Regeneration at email@example.com
This position requires bioengineering expertise and skills to catalyze collaborative projects with cardiovascular sciences, engineering, nanotechnology and clinical teams. The following include relevant areas of investigation:
- Novel minimally invasive methodology for endovascular, perivascular, myocardial or pericardial delivery of cells or bioengineered tissues
- New biomaterials for tissue engineering, including those with shape memory, surface switching, drug eluting, or biodegradable properties
- Mechanisms of release from polymeric delivery systems with concomitant nanostructural analysis using AFM and mathematical modeling
- Applications of these systems including the development of effective long-term delivery systems for small molecules, growth factors, or RNA-based agents that modulate cardiovascular processes
- Controlled release systems that can be magnetically, ultrasonically, optically, or enzymatically controlled so as to regulate release rates to optimally enhance cardiovascular processes
This individual will use molecular, electrophysiological, and imaging tools to interrogate the contractile and electrical properties of isolated cardiomyocytes, and will study the genetic regulation and/or cellular signaling pathways modulating these properties. A major thrust will be to understand genetic regulation and cardiomyocyte signaling in order to open new avenues for biological investigation and develop novel therapeutic strategies. The candidate will support other research teams by participating in the following ways:
- Analyze the function of bioengineered cardiac tissues
- Assess the fidelity of cardiomyocytes derived by directed differentiation from pluripotent or somatic cells
- Assess the effects of nanoparticles, small molecules and other therapeutics on cardiomyocyte function
Cell and Tissue Therapy
This individual will be skilled in translational research in cardiovascular stem cell applications, with expertise in pre-clinical models, as well as a keen understanding of the regulatory roadmap. The position requires knowledge of GLP methods for cell culture, and experience with methods of cell characterization to assess the viability and function of stem and progenitor cells, for example, FACS, mass cytometry, RNA seq, ChIP seq, DNA methylation and functional studies. This key recruit will help the basic scientists and bioengineers to envision the applications of their scientific insights, and to operationalize preclinical testing. This candidate will also work closely with clinical trial investigators, and facilitate the Center for Cardiovascular Regeneration mission of transitioning project from preclinical testing and proof-of-concept to first-in-human trials.
This key recruit will have extensive expertise in bioinformatics and statistics. The ideal candidate will be able to combine high volume data on expression, location and sequence to dissect the gene regulatory programs (e.g., microRNA, lncRNA, transcriptional factors and epigenetic modifiers) that underlie developmental and regenerative processes. This individual will be expected to provide the bioinformatic infrastructure for our scientific community, and will provide expertise in the analysis of microarray gene expression data (dChip) and ChIP-chip data (TileMap), and programs for mapping cis-regulatory motifs and modules (Cis-Module, Multi-module and Ortholog Sampler). This scientist will collaborate with other scientists at Houston Methodist to generate and analyze genetic datasets and protein-protein interaction maps to derive mechanistic insights into how specific pathways, complexes and proteins function in various cardiovascular processes. These bioinformatic analyses will provide new insights and directions of inquiry.
This scientist will study molecular events regulating early and late developmental decisions that instruct progenitor cells to adopt a cardiac or vascular cell fate. In many cardiovascular diseases, fetal gene programs are reactivated. Thus, unraveling every biological step in the embryonic development of the human cardiovascular system provides surprising insights as to what genes, RNAs or proteins can be targeted as a way to prevent or treat cardiovascular disease. Accordingly, the investigator will elucidate the network of transcriptional, translational and signaling events that control the early steps of cardiomyocyte or vascular differentiation and expansion. These insights will be used by the other investigators at Houston Methodist to, for example, optimize protocols for directed differentiation or transdifferentiation, or to determine which signaling pathways should be activated to enhance generation or maintenance of a bioengineered cardiovascular tissue.
Epigenetics and DNA Regulatory Control
This scientist will study regulation of cardiovascular phenotype and function at the epigenetic level. Investigations into epigenetic control of cardiovascular lineage will include key enzymes that post-translationally modify histone proteins (enzymes that add or subtract methyl, acetyl, phosphate groups; ubiquitin or sumo proteins) as well as DNA modifying enzymes. These epigenetic modifiers may place the chromatin into an ‘open configuration’ where transcriptional factors can activate gene expression or into a ‘closed configuration’ where gene expression is suppressed. Studies may include characterization of small noncoding RNAs such as microRNA, lncRNA and piwiRNA that play critical roles in the expression or stability of mRNA. This individual will collaborate with other Houston Methodist scientists in the following ways:
- Apply cutting edge techniques, such as single-cell assessments of DNA methylation and epigenetic markings to assess the ‘epigenetic memory’ of transdifferentiated cells
- Document the epigenetic fidelity after reprogramming and passaging of cells
- Confirm the epigenetic stability of cardiovascular cells after their incorporation into bioengineered matrices
Genetics and Genomic Engineering
This individual will have mastered the lexicon of genetic mutations and variants involved in cardiovascular disease, and will wield techniques in genetic engineering that can correct genetic variants, such as TALENS, Zinc finger nucleases, and CRISPR/Cas. Working with Houston Methodist biologists and our cell therapist, the genetic engineer may participate in the following ways:
- Correct or enhance stem and progenitor cell function for therapeutic cell delivery
- Collaborate with the nanotechnologists to develop new genetic tools
- Interact with the computational biologist to understand the effect of an induced genetic mutation on the expression or regulation of the network of related genes involved in cardiovascular functions
Progenitor and Stem Cell Biology
These individuals will generate new insights into the nature and regulation of cardiac and vascular stem and progenitor cells. Their complementary skill sets and knowledge will encompass the fields of embryonic stem cells, induced pluripotent stem cells, adult stem cells, transdifferentiation of somatic cells to cardiovascular lineage and cell-cell or cell-matrix interactions in tissue engineering. They will demonstrate facility with a range of molecular and cellular technology including the following:
- Quantitative DNA and RNA analyses
- Phosphoproteomics and metabolomics
- Stem cell culture and differentiation
- Use of functional assays and pre-clinical models from zebra fish to murine models.
They will elucidate the genetic determinants and signaling pathways involved in the reprogramming of somatic cells to pluripotency or to cardiovascular lineage. In collaborating with the other teams, they will apply cutting edge techniques in reprogramming and directed differentiation to generate cardiac and vascular cells for studies of pathobiology of inherited cardiovascular diseases; for preclinical studies of regenerative therapies; or for integration into bioengineered conduits or pumps.
Endothelial and vascular smooth muscle cell signaling and function will be the domain of this scientist, who may be particularly interested in angiogenesis, endothelial regeneration, vascular smooth muscle growth and/or interaction of the endothelium with the circulating blood elements. This scientist will delve deeply into genetic, epigenetic, transcriptional, and/or post-translational mechanisms of vascular function and phenotype. Insights derived from this scientist will be expected to lead to new avenues for small molecule, gene or cell therapies. In collaborating with the other Houston Methodist scientists, this individual will be able to assess the structure/function of bioengineered vessels; test the integrity of the microvasculature in a bioengineered tissue; analyze the interaction of circulating nanoparticles with the vessel wall; and to characterize the effect of genetic variants or mutations on vascular function.
These individuals will maintain clinical practice with half of their time dedicated to clinical research in regenerative therapies for cardiac or vascular diseases. The ideal candidates will have experience in first-in-human and Phase I-III clinical trials, and will be fully conversant with FDA guidelines for drug, device and cell therapies (one trialist focus on devices, the other on pharmacotherapy and stem cell trials). The scope of work will include studies funded by NIH, NGOs or industry. Each individual will be expected to participate in and organize regional, national or international consortia of investigators performing studies in cardiovascular regeneration, and to develop a database and biobank that leverages the patient volume of Houston Methodist. Each individual will also work closely with Houston Methodist physicians and scientists who are developing new therapies and devices, in an effort to help them accelerate entry into clinical trials.