Sorin Fedeles, PhD, MBA
Biography
Research & Publications
News
Biography
Leading a program focused on elucidating the impact of unfolded protein response (UPR) pathways modulation on the progression of Autosomal Dominant Polycystic Kidney Disease (ADPKD) using cellular, biochemical, genetic, and pharmacological approaches.
Employing whole-genome CRISPR/Cas9 forward screens coupled with single-cell RNAseq to identify new targets for ADPKD. Developed a novel proof-of-concept model to examine the role of ER protein folding in modulating the progression of ADPKD due to Pkd1 missense mutations. Characterized a novel genetic mouse model of tubulo-interstitial kidney disease. Initiated and managed a collaboration with a bio-engineering group at MIT to test/develop compounds for the treatment of ADPKD. Based on this, put together grant applications that have led to ~$2.6 million in federal and private funding from the Department of Defense (DoD) and the PKD foundation with a method-of-use patent issued.
Responsibilities include managing research staff, writing grants/manuscripts, budget oversight, teaching, serving as a peer-reviewer on grants and journal submissions, and disseminating research via national/international conferences.
Principal Investigator on past and current funded grants (accepted or declined) totaling ~$5.2 million from NIH (RO1-declined; P&F), DoD (Discovery and IIRA), and the PKD Foundation.
Currently serving as Executive Director of the Polycystic Kidney Disease Outcomes Consortium at Critical Path Institute.
Education & Training
- MBAYale School of Management, Healthcare (2016)
- Postdoctoral AssociateYale School of Medicine (2015)
- PhDYale University, Genetics (2010)
- MSYale University, Biological and Biomedical Sciences (2007)
Activities
- Modulation of hypomorphic polycystin-1 species in vivo ameliorates ADPKD progressionVirtual meeting 2023PKD RRC Symposium
- What Does Patient-Focused Drug Develoment Look Like in Rare Diseases?Washington, DC, United States 2023Rare and Orphan Disease Conference
- Clinical Trial Simulator Tools for modelling rare disease progressionWashington, DC, United States 2023Rare and Orphan Disease Conference
- Polycystic Kidney Disease Outcomes Consortium (PKDOC) 2.0 activities updateWashington, DC, United States 2023Rare and Orphan Disease Conference
- Advancement of Drug Development Tools for Polycystic Kidney Disease (PKD) as Told Through the PKD Outcomes Consortium StoryVirtual Conference 2023Joint Conference by FDA Center for Drug Evaluation and Research (CDER) and the Johns Hopkins University’s Center of Excellence in Regulatory Science and Innovation (JHU CERSI)
- Clinical trial simulator tool development for ADPKDOrlando, FL, United States 2022PKD Outcomes Consortium (PKDOC) Annual Meeting
- The role of XBP1 in modulating ADPKDLisbon, Lisbon, Portugal 2022FASEB ADPKD Meeting
- Genetic mechanisms of ADPKDBoston, MA, United States 2022Vertex Pharmaceuticals Invited Lecture
- Genetic models of ADPKDVirtual lecture 2022Polycystic Kidney Disease Outcomes Consortium Conference
- UPR pathways in ADPKDVirtual lecture for U. Colorado Denver PKD Center faculty 2021University of Colorado PKD Center Lecture
- Role of protein folding in modulating ADPKD disease progressionBoston, MA, United States 2019Harvard PKD Center Symposium
- Role of XBP1 in ADPKDSantiago de Compostela, GA, Spain 2019Spanish Society of Human Genetics Meeting
- Enhanced protein folding via XBP1 activation ameliorates ADPKD due to PC1 misfoldingSan Diego, CA, United States 2018Annual meeting for the American Society of Nephrology
- Endoplasmic Reticulum stress and the unfolded protein response in ADPKDBig Sky, MT, United States 2017FASEB ADPKD Meeting
- UPR in ADPKDChicago, IL, United States 2016Annual meeting for the American Society of Nephrology
- The role of XBP1 in Polycystin-1 folding and maturationKansas City, MO, United States 2016Kansas University Medical Center, Kansas City, MO.
- Genetic interaction between Sec63 and Xbp1 regulates Ire1 activity and polycystic disease progression.Baltimore, MD, United States 2015Nephrology and Therapeutics
- 11β is a novel compound that inhibits disease progression in models of Autosomal Dominant Polycystic Kidney DiseaseAtlanta, GA, United States 2013American Society of Nephrology Meeting
- The molecular and genetic interaction between the Ire1-Xbp1 unfolded protein response (UPR) pathway and Sec63 regulates polycystin-1 (PC1) protein processingNice, Provence-Alpes-Côte d'Azur, France 2013Sophia Antipolis, CNRS Institute of Molecular Pharmacology
- The most conserved pathway of the unfolded protein response (UPR) controls the Sec63p-dependent cystogenesisSaarlouis, SL, Germany 2013Saarland University invited lecture
- Glucosidase II activity represents a novel urine biomarker in the detection of Autosomal Dominant Polycystic Liver Disease (ADPLD) due to mutations in PRKCSHPhiladelphia, PA, United States 2012American Society of Nephrology Meeting
- Ire1- Xbp1 unfolded protein response (UPR) pathway is a genetic and molecular regulator of cystogenesis through a polycystin-1 (PC1) dependent mechanism.Philadelphia, PA, United States 2011American Society of Nephrology Meeting
- Sec63 is a modulator of autosomal recessive polycystic kidney disease (ARPKD).San Francisco, CA, United States 2008American Society of Nephrology Meeting
- Trafficking of Polycystin-1 is altered in autosomal dominant polycystic liver disease (ADPLD)Philadelphia, PA, United States 2007American Society of Nephrology Meeting
Honors & Recognition
| Award | Awarding Organization | Date |
|---|---|---|
| Investigator Initiated Research Award | Department of Defense | 2021 |
| RO1 Research Grant (Declined) | NIH | 2021 |
| Discovery Award | Department of Defense | 2020 |
| Pilot and Feasibility Award | Yale O'Brien Center | 2020 |
| Young Investigator Career Development Award | Polycystic Kidney Disease Foundation | 2019 |
| Polycystic Kidney Disease Foundation Grant | PKD Foundation | 2016 |
Professional Service
| Organization | Role | Date |
|---|---|---|
| National Institute of Health (NIH) | Early Career Reviewer (ECR) for the March 2023 PBKD study section. PBKD reviews basic, translational and clinical research R01/R21 applications involving acute and chronic kidney diseases. | 2022 - 2023 |
| Frontiers in Medicine | Guest editor for "Podocyte and Tubule - OPATHIES in Kidney Disease" series published in Frontiers in Medicine. Sourced innovative content, selected peer-reviewers and managed the entire life-cycle of accepted manuscripts. | 2021 - Present |
| Scientific Reports | Invited reviewer | 2020 - Present |
| Polycystic Kidney Disease Foundation | Selected reviewer for PKD Foundation Research Grants. | 2019 - 2021 |
| Kidney International | Invited reviewer | 2019 - Present |
| FASEB Journal | Reviewer | 2018 - Present |
| Journal of the American Society of Nephrology | Invited reviewer | 2015 - Present |
| Kidney Research UK | Reviewer for Kidney Research UK research grants. | 2014 - Present |