Postdoctoral Researcher

Union: Non-Union
Number of Vacancies: 1
Department: Cardiovascular Research
Reports To: Principal Investigator
Location: Toronto General Hospital, UHN
Shifts: Days
Hours: 37.5 hours per week
Status: Temporary Full-Time
Closing Date: January 9, 2025

Position Summary

The laboratory of Dr. Mansoor Husain is seeking a talented and highly motivated Postdoctoral Fellow to join our research team to help lead a recently funded Canadian Institutes of Health Research (CIHR) Project investigating the role of mitochondrial metabolism in heart failure pathogenesis and treatment.

Our lab is internationally recognized for investigating the molecular mechanisms of cardiovascular diseases with a focus on identifying new therapeutic targets. Husain lab has played a foundational role in unraveling the cardiovascular mechanisms of action of glucagon-like peptide-1 (GLP-1) peptides and related drugs [see NEJM 2019, PMID: 31185157 and JCI 2020, PMID: 31985487]. Our research has direct clinical relevance and has been widely cited by the global cardiovascular and metabolic disease research communities.

For the right individual, this is an exceptional opportunity to launch an academic career as part of a highly collaborative, well-funded and -supported research team. You will work alongside leading experts in cardiology, metabolism, genetics, and translational medicine, positioning yourself for success as a future independent researcher.

The Husain Lab is embedded within the Ted Rogers Centre for Heart Research, a world-leading cardiovascular research program that brings together scientists, clinicians, and engineers united by a mission to solve complex problems in heart disease. In this environment, Husain Lab enjoys highly collaborative interactions with world-leading experts in  a variety of disciplines, and unparalleled access to cutting-edge resources and facilities including advanced cardiac phenotyping (high-resolution echocardiography, invasive hemodynamic measurements), transgenic and conditional mouse models (tissue-specific and inducible knockout lines), metabolic assessment platforms (isolated perfused heart preparations, substrate oxidation measurements) and mass spectrometry capabilities for post-translational modification analysis and untargeted metabolomics. We utilize state-of-the-art molecular biology tools, cell culture models, and biochemical assays and have access to dedicated bioinformatics and statistical support.

Why Join This Lab for Career Development?

1. Learn cutting-edge research methodologies in cardiac phenotyping, genetic models, and translational research that are highly valued in academic medicine and industry
2. Build a strong collaborative network through interaction with leading experts in cardiovascular pathophysiology, proteomics, metabolomics, and translational science.
3. Contribute to publications in high-impact journals that will establish your research credentials and academic potential
4. Access mentorship and career guidance from an established investigator with a strong track record of training fellows who have gone on to independent academic positions
5. Work on research with clinical translational potential, positioning your work for future grant funding and academic advancement
6. Develop independence through increasing responsibility for experimental design, project leadership, and scientific writing

Position Details: CIHR-Funded Project

The successful candidate will contribute to a recently funded Canadian Institutes of Health Research (CIHR) Project entitled "Role of Mitochondrial Trifunctional Protein (MTP) in Heart Failure." This new research program aims to understand whether MTP, a key regulator of fatty acid oxidation, plays a causal role in heart failure development and whether it represents a viable therapeutic target.

The project integrates three interconnected scientific aims: (1) characterizing MTP expression, post-translational modifications, and enzymatic activity across distinct heart failure models; (2) determine causality through tissue-specific and temporal genetic deletion of MTP in cardiomyocytes and endothelial cells; (3) evaluate therapeutic targeting of MTP using novel GLP-1 metabolites.

The project employs multiple complementary model systems of heart failure (post-myocardial infarction ischemic heart failure, transverse aortic constriction pressure-overload heart failure, and obesity/hypertension-induced heart failure with preserved ejection fraction) as well as advanced metabolic and cardiovascular phenotyping at the whole animal organ, and cellular levels.

Key Responsibilities

• Generate and characterize mouse models of cardiovascular disease and heart failure and conduct advanced cardiac phenotyping, including high-resolution transthoracic echocardiography (structure and systolic/diastolic function), invasive hemodynamic measurements (LV pressure-volume analysis) with measurements of ejection fraction, cardiac output, and strain analysis.
• Be able to learn surgical procedures for generating mouse models, including permanent coronary ligation, transverse aortic constriction, and tissue/organ harvesting.
• Oversee breeding, genotyping, and maintenance of transgenic and conditional knockout mice, including inducible tissue-specific knockout lines.
• Execute established enzyme kinetic assays for MTP, including optimization of protein extraction, NADH-based activity measurements, and Western blots.
• Have the opportunity to learn and conduct mass spectrometry-based analyses of post-translational modifications and metabolomic markers, as well as learn and conduct isolated perfused heart experiments to assess cardiac energy substrate metabolism (rates of glycolysis, glucose oxidation, fatty acid oxidation, and ketone body oxidation).
• Cell culture experiments on freshly isolated mouse cardiomyocytes and endothelial cells derived from mouse models are also proposed.
• This position allows meaningful contributions to the development of experimental design and develop independence in project management, manuscript preparation, scientific writing, and the maintenance of detailed laboratory records to ensure compliance with animal care standards.

• MD (within the last 10 years), or PhD (within the last 5 years) in cell and molecular biology, biochemistry, cardiovascular biology, metabolism, or related fields.

Desired Experience and Technical Skills

Mouse models of cardiovascular and/or metabolic disease:

• Hands-on experience with mouse models of obesity, diabetes, hypertension and more specifically heart failure (post-MI, TAC, or other relevant models) including transgenic and knockout mouse management, breeding, and genotyping (PCR) are vital.
• Technical background in mouse cardiac physiological, histological and biochemical phenotyping – ideally including transthoracic echocardiography and invasive hemodynamic assessments (such as pressure-volume analysis, ejection fraction, cardiac output, global longitudinal strain, diastolic function assessments) are recommended.

Proficiency in biochemical and metabolomics techniques:

• Collaborative expertise is in place for the candidate to conduct and interpret gas chromatography-mass spectrometry (GC-MS), liquid chromatography-mass spectrometry (LC-MS), and analyze untargeted metabolomic data.
• Hands-on experience with enzyme kinetic assays and biochemical substrate assays as well as cellular flux analysis or bioenergetics assessments (Seahorse or similar platforms) is preferred.
• Experience with isolated organ perfusion techniques (particularly isolated heart preparations) and substrate oxidation measurements would be an asset.

Molecular biology and protein analyses:

• Expert-level proficiency is required in tissue- and cell-protein and RNA extractions and the ability to design and troubleshoot assays such as quantitative real-time PCR, Western blot, ELISA, and other immunoassays.
• Experience with protein sample preparations for mass spectrometry and analysis of proteomics data is desirable, with strong collaborative expertise available.

Data analysis and bioinformatics:

• Proficiency with statistical software (R, GraphPad, Prism, or equivalent) and the ability to perform appropriate statistical analyses and interpret results is essential.
• Experience with bioinformatics tools for ‘omics’ level data analysis is preferred.
• High level competency with data visualization and figure preparation for scientific publications is a must.

Professional competencies:

• Excellent organizational and time-management skills with ability to manage multiple projects simultaneously.
• Strong written and verbal communication skills, including ability to present data to scientific peers. Demonstrated ability to work independently and as part of a collaborative team.
• Meticulous attention to detail and commitment to scientific rigor.
• Proven track record of peer-reviewed publications demonstrating scientific productivity and impact. Problem-solving ability and adaptability when troubleshooting experiments.
• Commitment to continuing education and staying current with the literature in cardiovascular metabolism.
• Teaching and mentoring experience is recommended to take full advantage of our learning environment.

Position Benefits and Career Development Support

• Mentorship from an established investigator with extensive experience training postdoctoral fellows for academic careers.
• Support for grant writing and career development planning.
• Opportunities to present at national and international conferences.
• Access to professional development resources through UHN and University of Toronto.
• Competitive salary commensurate with CIHR postdoctoral fellowship standards and experience.
• Comprehensive health and dental benefits.
• Collaborative research environment with access to core facilities and collaborator networks.

Application Instructions

Interested candidates should submit the following materials:

1. Cover letter (2 pages) outlining your research experience and specific expertise relevant to this position. Your fit for this particular project and rationale for joining the Husain lab. Your career goals and how this position aligns with your trajectory toward independent research
2. Curriculum Vitae highlighting relevant research experience with emphasis on techniques listed in the qualifications. Your full list of publications and metrics (h-index, citation count if available), including presentations at conferences, seminars as well as honours, awards, and memberships [if any] in professional societies.
3. Contact information for three professional references (e.g. Ph.D. thesis supervisor, other research advisors, or senior colleagues familiar with your research capabilities). Please include the referee's name, title, institution, email, and phone number. Consider identifying at least one referee who can speak directly to your technical skills

Why join UHN?

In addition to working alongside some of the most talented and inspiring healthcare professionals in the world, UHN offers a wide range of benefits, programs and perks. It is the comprehensiveness of these offerings that makes it a differentiating factor, allowing you to find value where it matters most to you, now and throughout your career at UHN.

• Competitive offer packages
• Government organization and a member of the Healthcare of Ontario Pension Plan (HOOPP https://hoopp.com/)
• Close access to Transit and UHN shuttle service
• A flexible work environment
• Opportunities for development and promotions within a large organization
• Additional perks (multiple corporate discounts including: travel, restaurants, parking, phone plans, auto insurance discounts, on-site gyms, etc.)

Current UHN employees must have successfully completed their probationary period, have a good employee record along with satisfactory attendance in accordance with UHN's attendance management program, to be eligible for consideration.

All applications must be submitted before the posting close date.

UHN uses email to communicate with selected candidates.  Please ensure you check your email regularly.

Please be advised that a Criminal Record Check may be required of the successful candidate. Should it be determined that any information provided by a candidate be misleading, inaccurate or incorrect, UHN reserves the right to discontinue with the consideration of their application.

UHN is an equal opportunity employer committed to an inclusive recruitment process and workplace. Requests for accommodation can be made at any stage of the recruitment process. Applicants need to make their requirements known.

We thank all applicants for their interest, however, only those selected for further consideration will be contacted.