The missions of the Cardiology Division are patient care, teaching, basic and clinical research, and public service within the specialty of cardiovascular medicine. The Translational Cardiac Stem Cell Program and Laboratories (TCSCP) is housed within the Cardiology Division. The goal of the TCSCP is to combine and convert advances made in the basic bio-medical sciences and technology, together with stem cell biology, for developing drugs to treat serious diseases in patients with unmet medical need.
This position is for scientists who are interested in translational research, aiming to bring discoveries made in the lab towards therapeutic use in the clinics. The projects are related to exploiting molecular basis of disease for detecting and developing novel therapeutics. Diseases of interest include cancers, neurodegenerative diseases primarily. Other diseases include stroke and cardiovascular disease. Projects involve cross-disciplinary approaches in studying diseases that share common molecular pathologies including, but not limited to, aging, neurodegenerative diseases, cancers and cardiovascular disease. Projects involve investigating novel cellular and molecular pathways related to aforementioned diseases. These pathways will be exploited in developing assays for high throughput drug screening.
The TCSCP program seeks an outstanding scientist with a strong cell and molecular biology background to join our research team. The successful candidate will be involved in a cross-disciplinary program to translate scientific finding into discovering and developing therapeutics for treating numerous diseases including neurodegeneration, cancers, stroke, ischemic heart disease, and other diseases. The successful candidate will be investigating novel disease and drug-induced cellular pathways with the goal to specifically modulate the pathways related to drug action as well as disease causation. The successful candidate will collaborate with the high throughput screening (HTS) scientist to exploit his/her findings in developing assays for HTS. This position requires a very collaborative, team player oriented individual.
In summary, the candidate will:
- Develop assay for and perform automated high throughput screening (HTS) to discover new drugs.
- Characterize novel intracellular pathways in form of ‘lead-pathway’, and optimize cell-based pathway assays in vitro models of primary cells, IPS-derived cells and cell lines, to be exploited in high throughput screening (HTS).
- Develop and characterize genetically modified cell lines for pathway discovery assays, and new target evaluation.
- Perform cell engineering (overexpression, knockout, fluorescent marked proteins/overexpression) for implementing in HTS assays.
- Work with cross-disciplinary research team to discover and characterize inter-related pathways for developing the multiple inter-related pathways into lead target candidates that modulate cell fate signaling, with a focus on cancers, neurodegenerative diseases, heart disease and stroke.
- Present results and reports within a cross-disciplinary team environment.
- Provide scientific input across all TCSCP projects.
- Work very closely with the Associate Director.
In detail, the candidate will:
- Ensure that chemical, controlled, and expired substances inventory is performed. Schedule lab meeting.
- General cell culture/cell biology techniques: cell maintenance (freezing, splitting, media preparation). Immunocytochemistry and immunohistochemistry staining assays. Cell transfection assays (viral and non-viral). Tissue processing and handling of biological specimen for histological studies
- Specific cell culture/cell biology/molecular biology techniques: primary cell culture preparation from dissected tissues or biopsies, such as, but not limited to the heart and brain to generate and culture brain/cardiac derived cells (stem cells, progenitor cells). IPS-derived cells from patient samples, and/or disease-model samples. Immunoblot analysis. ELISA based assays. Perform immunological assay such as ELISA in human and animal blood. Angiogenesis assays. Cell death assays. FACS assays. Protein interaction assays, co-immunoprecipitation, overexpression studies, plasmid construction/gene cloning/cDNA cloning. IPS-technology to create cells of choice. Modulating/engineering cells via genetic manipulation in vitro systems. For example using CRISPR, viral vectors, RNAi, shRNA, or related methods. Modulating cellular pathways via pharmacological means. Performming DNA-Damage based assays to study corresponding pathways
- Perform protein quality control assays, cellular stress assays, FACS-based assays, multi-well plate based assays (fluorescent, staining, proliferation, cell cycle assays such as with 384 or higher well plates). Perform protein arrays (pathway arrays, kinase arrays, cytokine arrays)
- Assist with and/or perform high throughput drug screening in cell-based assays
- Develop various assays for high throughput drug screening
- Perform general standard molecular biology techniques (i.e. Western blot analyses, ELISAs, qPCR, etc).
- Specialized techniques: FACS analysis and sorting. Confocal microscopy. Immunoprecipitation (IP) and chromatin immunoprecipitation (ChIP) assays.
- General molecular biology techniques: cloning, plasmid preparation, PCR, RTPCR, qPCR. Perform basic molecular and biochemical assays for RNA/DNA detection using PCR, RT-PCR and Western Blotting, isolation of RNA/DNA, and protein from cells and animal tissue. Characterization of cells lines, including but not limited to: performing FACS analysis to define cell markers, performing migration assays, viability analysis, apoptosis and senescence assay.
- Specific molecular biology techniques: generation of fluorescent and non-fluorescent tagged fusion protein plasmid constructs for expression and localization studies/pathway studies/generation of cells for HTS. miRNA based techniques and assays.
- Assist in analyzing and writing up results in conjunction with the PI. Recommend changes to the protocol as indicated. Meet with the PI and other research staff at designated times to review results and discuss protocol and research direction. Teaching, supervising and mentoring others in the lab.
- PhD in cell biology/molecular biology or a related discipline, with experience (industry or academic experience- preferentially both) in HTS, robotic method generation, machine learning, or related areas.
- Outstanding understanding of cellular pathways related to normal function versus disease function versus drug effect.
- Deep scientific expertise and/or understanding in multiple disciplines including medicinal-chemistry, cellular and molecular biology, pharmacology, and screening technologies and assays
- Demonstrated proficiency in:
- Molecular basis of disease
- Cell-based screening assays for High-throughput assay development (HTS) to detect lead drug-compounds (high-throughput imaging and plate reader assays).
- Programming, operating, maintaining, troubleshooting, calibrating automated/robotic instrumentations
- Robotic/automated laboratory apparatus for running high throughput assays.
- Design/setting up robotic methods and algorithm programming for high throughput screening involving dose response and drug-combination studies, screen-analysis of assays
- Modulating cellular pathways by genetic and pharmacologic means
- Expertise using methods such as immunofluorescence staining and microscopy, luminescence, fluorescence based assays to analyze cell-output data. Demonstrated proficiency in implementing these methods in designing assays for High Throughput Screening.
- Demonstrated proficiency in cell and molecular biology techniques including:
- Immune-histological staining (fluorescent/non-fluorescent)
- Modulating/engineering cells via genetic manipulation in vitro systems. For example using CRISPR, viral vectors, RNAi, shRNA, or related methods.
- Cell death assays
- DNA-Damage based assays, protein degradation assays
- FACS-based assays
- Protein arrays (pathway arrays)
- Western blot analyses, ELISAs, qPCR
- IPS (induced pluripotent stem cell) technology/experimentations
Demonstrated proficiency with:
Machine learning with respect to drug screening
Modulating pathways related to:
- Neurodegenerative diseases such as Alzheimer’s, Parkinson’s, Huntington’s
- Cardiovascular disease
Email CV directly to Kurosh Ameri, PhD, Associate Director of TCSCP, at [email protected]