Job DescriptionTitle: Post-doctoral FellowSalary: $77,786.41Department: Medicine/NephrologyPhysical work location: One Gustave L. Levy Place, Annenberg 23, New York, NY 10029Name PI or Supervisor: (include phone and email) Kristin Meliambro, MD, kristin.meliambro @mssm.edu (Cjiiang.he@mssm.edu)Web link to Department: https://icahn.mssm.edu/about/departments/medicine/nephrologyAdministrative Contact: Irene Beaulieu, Irene.Beaulieu@mssm.edu , 212-241-8004QualificationsEducational and other Requirements for the position: MD or PhD degree with 2-3 years of relevant laboratory experienceExperience Required: 2-3 years of bench-based laboratory workGoals/Outcomes of the Research Project:Our long-term research goal is to elucidate critical signaling pathways that disrupt podocyte cytoarchitecture in order to identify targets for therapeutic intervention for glomerular diseases. Our project goals include: validation of predicted upstream regulators of WWC1/ KIBRA expression and identification of novel regulators via Chip-Seq and ATAC-seq analyses, define the biomechanical sequelae of KIBRA-mediated podocyte structural disruption, investigate downstream KIBRA non-canonical regulation of TEAD 1-4 and the effects of LATS kinase depletion in vitro and in vivo, and test whether novel small molecule LATS inhibitors and TEAD agonists can reverse or mitigate hyperglycemia-mediated podocyte injury in vitro and diabetic kidney disease in BTBR ob/ob mice.Compensation StatementThe Mount Sinai Health System (MSHS) provides a salary range to comply with the New York City Law on Salary Transparency in Job Advertisements. The salary range for this role is $73,588.00 - $80,000.00 Annually. Actual salaries depend on a variety of factors, including experience, education, and hospital need. The salary range or contractual rate listed does not include bonuses/incentive, differential pay or other forms of compensation or benefits., 036 - Renal MSH - ISM, Icahn School of MedicineEOE Minorities/Women/Disabled/VeteransThe Mount Sinai Health System is an equal opportunity employer. We comply with applicable Federal civil rights laws and does not discriminate, exclude, or treat people differently on the basis of race, color, national origin, age, religion, disability, sex, sexual orientation, gender identity, or gender expression. We are passionately committed to addressing racism and its effects on our faculty, staff, students, trainees, patients, visitors, and the communities we serve. Our goal is for Mount Sinai to become an anti-racist health care and learning institution that intentionally addresses structural racism.”ResponsibilitiesDetails of Research Project:Our work has identified KIBRA (encoded by WWC1 ) as a key regulator of glomerular disease progression, podocyte cytostructure, and podocyte injury via downstream LATS kinase activation and YAP inhibition in the canonical Hippo signaling pathway. However, little is known about the regulation of WWC1 /KIBRA expression, and therapeutic implications for KIBRA upregulation in FSGS and diabetic nephropathy remain unclear. Additionally, our preliminary data support non-canonical direct KIBRA downstream regulation of transcription factors TEAD 1-4. The objectives of this project are to define the regulators of WWC1 /KIBRA expression and function in podocytes, test non-canonical KIBRA-TEAD signaling, and to target LATS and TEAD as novel therapeutic strategies for KIBRA-mediated and diabetic podocyte injury. Based on our preliminary RNAseq analysis, our central hypothesis is that in podocytes, WWC1/KIBRA function in podocytes is repressed by the micro-RNA 200 family and regulated by transcription factors such as SOX4. In addition to canonical KIBRA regulation of LATS/YAP, KIBRA non-canonically directly suppresses TEAD 1-4 expression. Together, these downstream signaling events disrupt podocyte structural integrity and podocyte-glomerular basement membrane (GBM) adhesion, thereby promoting glomerular disease progression. The rationale for the proposed research is that testing novel regulators of KIBRA, non-canonical KIBRA signaling, and both novel canonical and non-canonical therapeutic approaches will significantly increase understanding of the mechanisms underlying glomerular disease progression and advance the quest for new selective treatments.Technical Duties: (include any protocols)
podocyte cell culture
treatment of cultured podocytes with injury agents and investigational drugs
cell fixation and IF staining
protein and RNA extraction
Western blot
qPCR
advanced microscopy imaging, including confocal and TIRF microscopy
microscopy imaging analysis using CellProfiler, Amarys, and other imaging software
mouse PCR genotyping
urine collection from mice
urine albumin ELISA and creatinine assays
blood collection from mice and glucometer testing
intraperitoneal administration of drugs
retrocardiac perfusion of mice
kidney harvesting for protein/RNA extraction and tissue fixation
kidney tissue IF and IHC staining
experimental data analysis
preparation of figures for presentation at lab meeting and for manuscript drafts
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At Mount Sinai, our leaders strive to learn, empower others, and embrace change to further advance equity and improve the well-being of staff, patients, and the organization. We expect our leaders to embrace anti-racism, create a collaborative and respectful environment, and constructively disrupt the status quo to improve the system and enhance care for our patients. We work hard to create an inclusive, welcoming and nurturing work environment where all feel they are valued, belong and are able to advance professionally.Explore more about this opportunity and how you can help us write a new chapter in our history!“About the Mount Sinai Health System:Mount Sinai Health System is one of the largest academic medical systems in the New York metro area, with more than 43,000 employees working across eight hospitals, more than 400 outpatient practices, more than 300 labs, a school of nursing, and a leading school of medicine and graduate education. Mount Sinai advances health for all people, everywhere, by taking on the most complex health care challenges of our time — discovering and applying new scientific learning and knowledge; developing safer, more effective treatments; educating the next generation of medical leaders and innovators; and supporting local communities by delivering high-quality care to all who need it. Through the integration of its hospitals, labs, and schools, Mount Sinai offers comprehensive health care solutions from birth through geriatrics, leveraging innovative approaches such as artificial intelligence and informatics while keeping patients’ medical and emotional needs at the center of all treatment. The Health System includes approximately 7,400 primary and specialty care physicians; 13 joint-venture outpatient surgery centers throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and more than 30 affiliated community health centers. We are consistently ranked by U.S. News & World Report's Best Hospitals, receiving high "Honor Roll" status, and are highly ranked: No. 1 in Geriatrics and top 20 in Cardiology/Heart Surgery, Diabetes/Endocrinology, Gastroenterology/GI Surgery, Neurology/Neurosurgery, Orthopedics, Pulmonology/Lung Surgery, Rehabilitation, and Urology. New York Eye and Ear Infirmary of Mount Sinai is ranked No. 12 in Ophthalmology. U.S. News & World Report’s “Best Children’s Hospitals” ranks Mount Sinai Kravis Children's Hospital among the country’s best in several pediatric specialties. The Icahn School of Medicine at Mount Sinai is ranked No. 14 nationwide in National Institutes of Health funding and in the 99th percentile in research dollars per investigator according to the Association of American Medical Colleges. Newsweek’s “The World’s Best Smart Hospitals” ranks The Mount Sinai Hospital as No. 1 in New York and in the top five globally, and Mount Sinai Morningside in the top 20 globally.The Mount Sinai Health System is an equal opportunity employer. We comply with applicable Federal civil rights laws and does not discriminate, exclude, or treat people differently on the basis of race, color, national origin, age, religion, disability, sex, sexual orientation, gender identity, or gender expression. We are passionately committed to addressing racism and its effects on our faculty, staff, students, trainees, patients, visitors, and the communities we serve. Our goal is for Mount Sinai to become an anti-racist health care and learning institution that intentionally addresses structural racism.”EOE Minorities/Women/Disabled/VeteransCompensation StatementMount Sinai Health System (MSHS) provides a salary range to comply with the New York City Law on Salary Transparency in Job Advertisements. The salary range for the role is $72500 - $80000 Annually. Actual salaries depend on a variety of factors, including experience, education, and hospital need. The salary range or contractual rate listed does not include bonuses/incentive, differential pay or other forms of compensation or benefits.