Lab News
Congratulations on Lindsey starting her NIH T32 predoctoral fellowship on 7/1/2024!
Lindsey gave a poster presentation in the RNA Society Meeting 2024 in Edinburgh, UK on 5/31/2024.
Congratulations on Omar and Feng's graduation with their Ph.D.!!
Amazingly, their postdoctoral mentors (Drs. Kevin Weeks and Jin Billy Li) coincidentally published their opinions on the future of RNA research in Cell Chemical Biology 31, January 18, 2024 11.
Voices: Challenges and opportunities in RNA biology
In the first of many thematic issues marking the 30th anniversary of Cell Chemical Biology, we highlight the contribution of chemical biology to RNA biology in a special issue on RNA modulation. We asked several leaders in the field to share their opinions on the current challenges and opportunities in RNA biology.
Peng will start his service as a standing member in the NIH MPPA study section from 7/1/2024 to 6/30/2028.
Welcome Jack Schwartz to join the lab on June 3rd as the 1st year BMB Program graduate student! He is interested in working on the development of RNA-based gene regulatory tools and therapeutics.
Welcome Yui Kawakami and Jiali He, who will join the lab as the lab technician and research specialist, respectively, starting on June 10th!
Welcome Uday Baliga to the lab as a postdoctoral fellow on April 16th!
Genetics Day 2024
Deb presented a poster for the lab on 5/13/2024.
Biomolecules MDPI
Join us for a special issue on "Recent Advances in the Role of Translation Machinery and Translational Control in the Cardiovascular System" in Biomolecules.
Edited by Dr. Peng Yao and Dr. Wei Guo
Deadline: October 1, 2024.
View more details: https://brnw.ch/21wID8K
Peng received the American Heart Association Established Investigator Award for 2024. Drs. EngSoon Khor (a former postdoctoral fellow interviewing for an independent faculty position in Malaysia) and Feng Jiang (a former Ph.D. student in the BMB Graduate Program) initiated and conducted this work.
Lindsey gave a poster presentation in the 19th URMC Dept. of B&B Annual Retreat on 3/11!
Congratulations to Jared for receiving an offer from the Ohio State University and SUNY Upstate PhD Program! He has also been interviewed at UofR Medical Center, University of Albany, and Penn State University and is looking forward to getting more offers!
Congratulations to Matt for receiving an invitation to start working in the pediatric cardiology department to care for kids with congenital heart diseases under the leadership of our close collaborator, Dr. George Porter! Good luck with Matt's application for the MD program! We welcome Matt to come back for a new round of research training in his future MD program as he wishes.
We are grateful for the two rotation Ph.D. students, Jack and Belal, who have worked with us for the last two months. We look forward to two new lab technicians, two graduate students, and one postdoc fellow joining us soon. Welcome Yui Kawakami to the lab as an undergraduate internship student starting on 3/18!
Our paper entitled "Cardiomyocyte-Specific Loss of Glutamyl-prolyl-tRNA Synthetase Leads to Disturbed Protein Homeostasis and Dilated Cardiomyopathy" was published online in Cells on 12/22/2023 (https://www.mdpi.com/2073-4409/13/1/35).
Abstract
Glutamyl-prolyl-tRNA synthetase (EPRS1), an aminoacyl-tRNA synthetase (ARS) ligating glutamic acid and proline to their corresponding tRNAs, plays an essential role in decoding proline codons during translation elongation. The physiological function of EPRS1 in cardiomyocytes (CMs) and the potential effects of the CM-specific loss of Eprs1 remain unknown. Here, we found that heterozygous Eprs1 knockout in CMs does not cause any significant changes in CM hypertrophy induced by pressure overload, while homozygous knockout leads to dilated cardiomyopathy, heart failure, and lethality at around 1 month after Eprs1 deletion. The transcriptomic profiling of early-stage Eprs1 knockout hearts suggests a significantly decreased expression of multiple ion channel genes and an increased gene expression in proapoptotic pathways and integrated stress response. Proteomic analysis shows decreased protein expression in multi-aminoacyl-tRNA synthetase complex components, fatty acids, and branched-chain amino acid metabolic enzymes, as well as a compensatory increase in cytosolic translation machine-related proteins. Immunoblot analysis indicates that multiple proline-rich proteins were reduced at the early stage, which might contribute to the cardiac dysfunction of Eprs1 knockout mice. Taken together, this study demonstrates the physiological and molecular outcomes of loss-of-function of Eprs1 in vivo and provides valuable insights into the potential side effects on CMs, resulting from the EPRS1-targeting therapeutic approach.
Congratulations to Omar and Feng for their thesis defense and graduation!
Omar will be joining Dr. Kevin Weeks's lab at UNC in January 2024, and Feng will be joining Dr. Jin Billy Li's lab at Stanford University in February 2024 as a postdoctoral fellow.
Our paper entitled "Secondary structures that regulate mRNA translation provide insights for ASO-mediated modulation of cardiac hypertrophy" was published online in Nature Communications on 10/3/2023 (https://www.nature.com/articles/s41467-023-41799-1).
Abstract
Translation of upstream open reading frames (uORFs) typically abrogates translation of main (m)ORFs. The molecular mechanism of uORF regulation in cells is not well understood. Here, we data-mined human and mouse heart ribosome profiling analyses and identified a double-stranded RNA (dsRNA) structure within the GATA4 uORF that cooperates with the start codon to augment uORF translation and inhibits mORF translation. A trans-acting RNA helicase DDX3X inhibits the GATA4 uORF-dsRNA activity and modulates the translational balance of uORF and mORF. Antisense oligonucleotides (ASOs) that disrupt this dsRNA structure promote mORF translation, while ASOs that base-pair immediately downstream (i.e., forming a bimolecular double-stranded region) of either the uORF or mORF start codon enhance uORF or mORF translation, respectively. Human cardiomyocytes and mice treated with a uORF-enhancing ASO showed reduced cardiac GATA4 protein levels and increased resistance to cardiomyocyte hypertrophy. We further show the broad utility of uORF-dsRNA- or mORF-targeting ASO to regulate mORF translation for other mRNAs. This work demonstrates that the uORF-dsRNA element regulates the translation of multiple mRNAs as a generalizable translational control mechanism. Moreover, we develop a valuable strategy to alter protein expression and cellular phenotypes by targeting or generating dsRNA downstream of a uORF or mORF start codon.
Welcome Deb and Matt to join Yao lab!
Dr. Debojyoti Das is a fresh PhD holder recently graduated from the Institute of Life Sciences, Bhubaneswar, India. He previously worked with Prof. Chandra Panda on circular RNA translation in metabolic syndrome (e.g., diabetes). Deb recently joined the lab on 8/17/2023. He will work on mRNA translation initiation in cardiac fibrosis.
Matthew Auguste, a 4th-year undergraduate student from the University of Rochester (major in Molecular Genetics), who worked in our lab as an intern student for nearly 3 years, returned and joined our lab as a lab technician starting on 8/28/2023. He will work on the biochemical characterization of PRRC2B function and mechanism as well as FAM210A genetic mouse model phenotyping.
Emily Bonanno, our summer research program undergraduate student from UofR, finished her exciting research study on identifying RNA-binding motifs in PRRC2B that regulates the translation of cell proliferation-related mRNAs and is involved in congenital heart defects and cancer when the function is inactivated or over-activated. She presented her poster in the final research symposium on 8/3/2023.
Our paper entitled as "FAM210A regulates mitochondrial translation and maintains cardiac mitochondrial homeostasis" has been published online in Cardiovascular Research on 8/1/2023 (https://doi.org/10.1093/cvr/cvad124).
Abstract
Aims
Mitochondria play a vital role in cellular metabolism and energetics and support normal cardiac function. Disrupted mitochondrial function and homeostasis cause a variety of heart diseases. Fam210a (family with sequence similarity 210 member A), a novel mitochondrial gene, is identified as a hub gene in mouse cardiac remodeling by multi-omics studies. Human FAM210A mutations are associated with sarcopenia. However, the physiological role and molecular function of FAM210A remain elusive in the heart. We aim to determine the biological role and molecular mechanism of FAM210A in regulating mitochondrial function and cardiac health in vivo.
Methods and Results
Tamoxifen-induced αMHCMCM-driven conditional knockout of Fam210a in the mouse cardiomyocytes induced progressive dilated cardiomyopathy and heart failure, ultimately causing mortality. Fam210a deficient cardiomyocytes exhibit severe mitochondrial morphological disruption and functional decline accompanied by myofilament disarray at the late stage of cardiomyopathy. Furthermore, we observed increased mitochondrial reactive oxygen species production, disturbed mitochondrial membrane potential, and reduced respiratory activity in cardiomyocytes at the early stage before contractile dysfunction and heart failure. Multi-omics analyses indicate that FAM210A deficiency persistently activates integrated stress response (ISR), resulting in transcriptomic, translatomic, proteomic, and metabolomic reprogramming, ultimately leading to pathogenic progression of heart failure. Mechanistically, mitochondrial polysome profiling analysis shows that FAM210A loss of function compromises mitochondrial mRNA translation and leads to reduced mitochondrial encoded proteins, followed by disrupted proteostasis. We observed decreased FAM210A protein expression in human ischemic heart failure and mouse myocardial infarction tissue samples. To further corroborate FAM210A function in the heart, AAV9-mediated overexpression of FAM210A promotes mitochondrial-encoded protein expression, improves cardiac mitochondrial function, and partially rescues murine hearts from cardiac remodeling and damage in ischemia-induced heart failure.
Conclusion
These results suggest that FAM210A is a mitochondrial translation regulator to maintain mitochondrial homeostasis and normal cardiomyocyte contractile function. This study also offers a new therapeutic target for treating ischemic heart disease.
Welcome Lindsey and Pandit to join Yao lab!
Lindsey Wainwright is a first year graduate student from Biochemistry & Molecular Biology PhD Program joining us as rotation student on 3/15 and decided to stay in our lab for her thesis research starting from 6/1/2023. She is studying "stress responsive regulation of translation initiation".
Dr. Madhuparna Pandit is a fresh PhD holder recently graduated from Indian Institute of Science, Bangalore, India. She previously worked with Prof. Sandeep M Eswarappa on translational readthrough mechanism of stop codon in a key neuronal protein coding mRNA. Pandit recently joined the lab on 7/5/2023. She will work on mRNA secondary structure and translational regulation of mRNA isoforms.
Emily Bonanno is a rising Senior and has been in the Yao Lab since September 2022. Emily has received an AHA-funded scholarship for her research this summer and was accepted into the UR School of Medicine and Densitry's Summer Scholars program. She will continue in our lab throughout her last year at UR. Her research interest includes a project identifying RNA-binding amino acid residues from a novel RNA-binding protein PRRC2B.
On 6/26/2023, Dr. EngSoon (Darren) Khor presented great work on eIF4G2 function in cardiac fibrosis in ACRE@ISHR-NAS Pre-Conference Symposium, Madison. Dr. Yao gave an invited featured lecture entitled "Translational control of cardiac pathophysiology: when mRNA meets the heart.
On 6/28/2023 Dr. Yao gave an conference talk entitled "Secondary structures that regulate mRNA translation provide insights for ASO-mediated modulation of cardiac hypertrophy" in the 42nd International Society for Heart Research-North American Section (ISHR-NAS), Madison.
Yao Receives Grant for Cardiac mRNA Research
Wednesday, May 24, 2023
Peng Yao, PhD, associate professor of Medicine and Biochemistry & Biophysics at the Aab Cardiovascular Research Institute and the RNA Center: From Genome to Therapeutics, has received a grant from the National Heart, Lung, and Blood Institute for his research project “uORF-mediated Translational Control of Cardiac Transcription Factor Expression.”
His project is focused on studying messenger RNA (mRNA) in relation to heart disease, which is the leading cause of morbidity and mortality in the US and the world. mRNA is responsible for creating proteins in the human body. Disease happens when there is too much “bad” protein or too little “protective” protein. Yao and his lab will study a specific protein factor called GATA4 and its mRNA, which is often over-produced in heart disease.
Understanding protein synthesis in cardiac muscle cells in normal physiology compared to cardiac muscle enlargement due to heart disease will help researchers develop novel ideas for preventive and therapeutic interventions. Yao has already discovered that GATA4 can be made in two forms: big and small. The big form can cause heart muscle cells to enlarge, but the small form can counteract those effects. He has identified a part of the GATA4 mRNA that acts as a “switch” to determine which protein form it generates. Similar to the COVID mRNA vaccine, a potential GATA4 mRNA-targeting RNA drug could instruct cells to produce specific proteins to prevent or treat heart disease.
This research grant is funded at over $2 million through March 2027.
Resource: https://www.urmc.rochester.edu/medicine/news/news.aspx#newsItem6524
Omar was presenting his PhD thesis work in CVRI trainee seminar on RNA drug development. He joined his force with Feng, another graduate student, to try to tackle a challenging question---how to deliver RNA inside cardiomyocytes.
Welcome Lindsey Wainwright to join our lab as a graduate student for her thesis research during 2023-2027!
Welcome back to Emily Bonanno in our lab for her summer scholarship research program! We are hoping to continue to attract such talented graduate and undergraduate students.
Congratulations to Matt on his undergraduate thesis defense on 4/21! Great job! Thanks for his thesis committee members Sia, Mitch and Dragony. It is much appreciated for Matt's research work in the lab for the last two years. We are looking forward to having Matt to join the lab as a pre-Med. student for another year hopefully!
Matt has received a prestigious UofR College Award on 5/2. Congrats to Matt!
JOURNAL ARTICLE
RNA binding protein PRRC2B mediates translation of specific mRNAs and regulates cell cycle progression
Feng Jiang, Omar M Hedaya, EngSoon Khor, Jiangbin Wu, Matthew Auguste, Peng Yao
Nucleic Acids Research, gkad322, https://doi.org/10.1093/nar/gkad322
Published: 01 May 2023
Feng's NAR paper was published online. This work followed up with Dr. Shinya Yamanaka's interesting work and hypothetical model of PRRC2-containing translation initiation complex for mouse embryonic stem cells (ESC) in PNAS in 2017 and the first time provided solid evidence of PRRC2B-mediated translational regulation via direct binding specific CU- and GA-rich cis-acting RNA elements on mRNA 5' untranslated regions. This translation pathway may synergize or complement with the classic eIF4E-eIF4G1 (mTORC1) pathway to control translation initiation of a selective cohort of mRNAs that encode cell cycle progression and protein homeostasis related proteins. It is well known that PRRC2B is highly expressed in a variety of human cancers and mutated with introducing premature termination codon in human congenital heart disease patients. There are still lots of mysteries to be explored such as PRRC2B's biological or physiological role in living organisms and its precise molecular mechanism and structural features in regulating translation initiation in cancer cells, ESC, and cardiovascular cell types.
Yao lab received a new NIH R01 funding from NHLBI to work on translational control mechanism mediated by uORF and secondary structure located in 5' UTR of cardiac mRNAs in order to develop RNA-based therapeutics to treat cardiac hypertrophy and/or fibrosis. We welcome new graduate students and postdoc research fellows to join our lab to continue with this exciting journey of fundamental science and drug development!
Congratulations to Bin! He will join the Cardiovascular Disease Research Insitute of Soochow University in May to establish his independent lab as a professor. Wish him all the best luck for his bright future!
Darren, Feng and Omar presented their posters in the 2023 Albany RNA Symposium on 3/16
We are appreciative of Omar Hedaya and Dr. EngSoon (Darren) Khor's research work in developing RNA-based therapeutics with collaborations of the Empire Discovery Insitute (EDI) in Western New York State and Novo Nordisk compnay in Denmark. We had a great meeting with EDI/Novo in person and on-line and shared our work progress. The industrial partners provided us constructive feedback that will further boost our research. See Linkedin poster from Novo.
Sebastian Beck Jørgensen(He/Him)
Senior Medical Advisor at the Novo Nordisk Bio Innovation Hub
The journey of developing transformational therapeutics helping humans living with chronic diseases all starts with identifying an innovation with a competitive edge, understanding the medical unmet it can resolve - and working with the best scientists and entrepreneurs. We have together with Ron Newbold, Michael Lark, PhD and the Empire Discovery Institute created the LeapRx program which aims at bridging academic research with pharma to reach this goal. I had the pleasure to team up with Dr Peng Yao and Dr Yongho Bae at U Rochester and U Buffalo to discuss new data and future research goals of our LeapRx collaborations. If you want to learn more about LeapRx, please reach out to me or Molly Mesko for additional information. Last but not least, thanks to Smitha James, Jeff Dunbar and their amazing team for hosting a productive day at the UB Innovation Hub.
Former Staff Scientist Dr. Kadiam Venkata Chinna joined Scriptr Global company to work on CRISPR-dCas13 RNA editing and circular RNA platform for developing novel therapeutics to treat a variety of human genetic diseases.
Venkata's Journal of Cardiovascular Development and Disease paper has been published online. He repurposed an FDA approved anti-fungal drug ciclopirox (CPX) for anti-fibrosis treatment in ischemic heart failure in a mouse myocardial infarction disease model. High throughput quantitative mass spectrometry analysis shows that ProPro-rich motif containing extracellular matrix proteins are significantly reduced by CPX-mediated inhibition of eIF5A hypusination.
Peng has a new Harold S. Geneen Charitable Trust Award Program for Coronary Heart Disease Research activated on 1/1/2023. We welcome new postdoc fellow and staff scientist to join our lab to start an exciting scientific research journey in RNA biology and cardiovascular disease!
Peng has received industrial funding from Empire Discovery Institute in New York State partnered with Novo Nordisk compnay from Denmark, the LeapRx Award to support a research program of development of RNA-based therapeutics to treat cardiac disease and fibrosis related disorders. Omar, a PhD student, is joining the force with Darren and an upcoming new postdoc fellow to develop RNA-based therapeutics to treat human diseases.
LeapRx Award program:
Session BASC.02 - Best of AHA Specialty Conferences: BCVS 2022
BCVS41 / 174 - Secondary Structure And Antisense Oligonucleotides Regulate Cardiac Messenger RNA Translation And Modulates Cardiomyocyte Hypertrophy
November 5, 2022, 11:00 AM - 12:00 PM
Best of Specialty Conferences, Science and Technology Hall, Level 3
Authors
Peng Yao, Univ of Rochester SMD, Pittsford, NY; Omar Hedaya, KADIAM VENKATA, feng jiang, Jiangbin Wu, Univ of Rochester, Rochester, NY; EngSoon Khor, Univ of Rochester SMD, Pittsford, NY
Disclosures
P.Yao: None. O.Hedaya: None. K.Venkata: None. F.Jiang: None. J.Wu: None. E.Khor: n/a.
Abstract
Translation of upstream open reading frames (uORFs) typically abrogates translation for the main ORF (mORF) and regulates protein expression. uORFs are present in nearly 50% of messenger RNA (mRNA) transcripts, but their impact and regulation on biological processes are understudied. Mining of ribosome profiling data from next-generation sequencing analysis of human and mouse hearts reveals that most translated uORFs reside within mRNAs of transcription factors, which play essential roles in cardiomyocyte (CM) development and growth. We show that the uORF start codon synergizes with an immediate downstream double-stranded RNA (dsRNA) element to activate uORF and inhibit mORF translation. Biochemical and genetic evidence support that this mechanism is utilized by mRNAs encoding multiple transcription factors such as GATA4 (GATA binding protein 4), encoding a master transcription regulator of CM differentiation and pathological hypertrophy. Intriguingly, a trans-acting regulatory factor, DEAD-box RNA helicase DDX3X, is involved in unwinding the dsRNA structure and promoting mORF translation. We develop two types of antisense oligonucleotides (ASOs) that mimic the unwinding or stabilizing of the dsRNA secondary structure, thereby suppressing or enhancing the translation of this uORF, respectively. Genetic or chemical inactivation of this GATA4 uORF using CRISPR-Cas9 or ASOs in human embryonic stem cells lead to enhanced differentiation into CMs and cellular hypertrophy. At the organismal level, short-term treatment of isoproterenol and surgery-induced cardiac hypertrophy mouse models with uORF-enhancing ASOs reduces GATA4 mRNA translation and antagonizes cardiac hypertrophy and remodeling. As a summary, this uORF-dsRNA element is a new tunable regulator of cardiac transcription factor mRNA translation and can be targeted to alter cellular and organismal phenotypes. Moreover, mechanism-based translation-manipulating ASOs can serve as promising biotechnological tools to regulate gene expression in vitro and in vivo and can be adapted to create novel RNA-based therapeutics.
In the Rustbelt RNA Meeting 2022 held on Oct. 14 2022 in Cleveland, Dr. EngSoon Khor presented his exciting work in translational control of cardiac fibrosis as a selected talk, and Feng Jiang, a graduate student, gave a poster presentation on a novel translation initiation regulatory factor in regulating cell cycle progression.
Omar presented his wonderful work in AAPS 2022 PHARMSCI 360 Conference on Oct. 16 in Boston.
Peng received the University Research Award starting at July 1, 2022
See University of Rochester news below.
https://www.rochester.edu/research/university-research-awards.html
Staff Scientist Dr. Kadiam Venkata Chinna's JCI Insight paper has been published online. Congrats!
Also, a video abstract has been posted in the website recently.
One postdoctoral assciate EngSoon Khor and two graduate students Omar Hedaya and Feng Jiang presented their reserach posters on the Genetics Day of UofR on May 16, 2022.
RNA Collaborative Seminar – University of Rochester, Center for RNA Biology, Feb 23, 2022
Peng has been promoted to Associate Professor.
Congratulations to Omar on receiving his Poster Award from the 26th RNA Society Annual Conference in August 2021! Hooray!
Congrats to Matt on finishing his AHA-sponsored summer scholarship program working in our lab on research about CRISPR-Cas9 system!
Photo: Poster presentation by Matt on 8/6/2021
Peng has given a talk on 7/23/21 about a novel strategy to develop RNA-based therapeutics with Dr. Steven Fox, the CEO of Alelos, Inc. for potential research collaborations.
Notes from Dr. Lynne Maquat:
Just to keep you informed of RNA Center activities, we had six presentations last Friday morning to entrepreneur Steve Fox, who flew in from NYC. Steve has been contacting me periodically about ongoing RNA-centric research, and I felt the time was right to begin in-person interactions. For this meeting, we used CVRI space, rather than space in Biochem & Biophysics for esthetic reasons. Presenters spanned Medicine, Biochemistry & Biophysics, and Pharm Phys and were: John Lueck, Mitch O’Connell, new hire Eric Wagner (official on board August 1st), Peng Yeo, Yi-Tao Yu, and Josh Munger.
Congratulations on Dr. Jiangbin Wu's receiving the Career Development Award from the American Heart Association that will start on July 1st, 2021 and being selected as a finalist of the Outstanding Early Career Investigator Award for the BCVS2021 Scientific session! His talk presentation will occur at 3:15-3:30PM on 8/24/2021.
Virginia Aswad, our lab technician, will join GreenLight Biosciences company in the near future to work on manufacturing RNA as agriculture and human health products. She has also received another job offer from Regeneron company as well. Congrats on her!
NEW RESEARCH FINDINGS PUBLISHED in 2020
Cardiovascular disease (CVD is the number one killer of human beings and have recently resulted even more human death in combination with COVID19 virus infection during the pandemic. As exemplified by the two recently FDA approved mRNA vaccines from Pfizer and Moderna companies, we are so excited that mRNA plus translation can make our own cells manufacture vaccine proteins to protect us from virus infections and relieve the burden for our cardiovascular system. Importantly, mRNAs can also produce therapeutic proteins via the translation process to fight against a variety of diseases including cardiovascular disease and cancer. Our research perfectly aligns with the goal and missions of these pharmaceutical companies in aiming to utilize or manipulate mRNA translation to treat human diseases.
In July 2020, we published our results in Circulation Research [1] about the function of an evolutionarily conserved, house-keeping enzyme glutamyl-prolyl-tRNA synthetase in cardiac fibrosis, and a Chinese medicine derived compound halofuginone in antagonizing fibrosis via inhibiting proline-rich protein translation. This compound was used for treating malaria infection and arrhythmia in ancient China for more than 2000 years. High dose of the drug can inhibit global protein synthesis via blocking the incorporation of proline amino acid, a building block of mRNA translation. Our data suggests that low dose of this drug actually can provide therapeutic benefit in heart disease treatment by mildly inhibiting translation of proline-rich proteins, which are mostly encoded by pro-fibrotic extracellular matrix transcripts in cardiac fibroblasts. Selective repression of expression of these fibrogenic proteins by knocking out one allele of Eprs gene in loss-of-function genetic mouse models or inhibiting enzymatic activity of EPRS protein, remarkably reduces cardiac fibrosis and hypertrophy, and partially restored cardiac function in heart failure mouse models.
On December 28th 2020, we had another paper published online in EMBO Molecular Medicine [2] showing that a cardioprotective small noncoding RNA, microRNA-574 (miR-574), plays important role in maintaining mitochondrial translation homeostasis and normal cardiac function via fine-tuning the expression of a novel mitochondrial translation regulatory factor FAM210A (family with sequence similarity 210 member A). Mitochondria are the power houses of living cells. They provide ATP as energy currency to support any biochemical reactions in our own body. Dysfunction of mitochondria caused by aberrant expression of mitochondrial proteins is known to trigger severe mitochondrial cardiomyopathy and heart failure. In this work, we used an miR-574 genetic knockout mouse model and transcriptome-wide gene expression profiling to discover that miR-574-FAM210A axis plays a critical role in maintaining optimal mitochondrial protein translation and protecting heart functions under cardiac stress conditions.
To confirm the relevance of EPRS and miR-574 in human heart failure, we collaborated with a cardiologist and physician scientist Dr. Wai Hong Wilson Tang from Cleveland Clinic to obtain human failing heart and non-failure tissue samples to measure the expression of EPRS and miR-574 and validated their relationship with human heart disease. A major challenge in these studies is to define the downstream molecular targets of EPRS and miR-574. With the extensive collaborative efforts from the University of Rochester Genomics Core, we performed the polysome profiling coupled with next generation RNA deep sequencing for halofuginone-treated, EPRS-inhibited fibroblast cells, and RNA-sequencing for miR-574 knockout mouse hearts, respectively. We successfully identified the target mRNAs of EPRS and miR-574 and discovered a number of novel therapeutic targets (such as SULF1 and FAM210A, respectively) for treatment of cardiac fibrosis and pathological remodeling.
Jiangbin Wu, Kadiam C Venkata Subbaiah, Li Huitong Xie, Feng Jiang, Eng-Soon Khor, Deanne Mickelsen, Jason R. Myers, Wai Hong Wilson Tang, and Peng Yao. Glutamyl-prolyl-tRNA synthetase regulates proline-rich pro-fibrotic protein synthesis during cardiac fibrosis. Circulation Research 2020 127:827–846
Jiangbin Wu, Kadiam C Venkata Subbaiah, Feng Jiang, Omar Hedaya, Amy Mohan, Tingting Yang, Kevin Welle, Sina Ghaemmaghami, Wai Hong Wilson Tang, Eric Small, Chen Yan, and Peng Yao. MicroRNA-574 regulates FAM210A expression and influences pathological cardiac remodeling. EMBO Molecular Medicine Online published (https://doi.org/10.15252/emmm.202012710)
A new Chapter was recently published in the book of THE ENZYMES. This chapter introduces the function and mechanism of aminoacyl-tRNA synthetases in cell signaling related to human diseases. We discuss about the role of EPRS and LeuRS in multiple cellular signaling pathways in great details.
Rustbelt RNA Meeting will be held on 10/23-24. https://rustbeltrna.org/2020/agenda.php
Omar Hedaya from our lab will present a talk at 3-3:15 PM on 10/23.
Session II: Plenary 2. Translational Control
uORF control of cardiac gene expression: Lessons learned from a single nucleotide that regulates cardiomyocyte biology
Omar received Silver Prize in RNA Essay Contest — Aug 27, 2020 12:14:56 AM
Welcome Virginia Aswad! — Aug 15, 2020 2:01:43 AM
Invited talk for Department of Medicine Grand Rounds — Aug 15, 2020 1:59:49 AM
Circulation Research paper published online — Jul 4, 2020 7:45:10 PM
BMB Faculty Peng Yao co-organizes 2019 Rustbelt RNA Meeting — Dec 26, 2019 2:54:27 AM
Congratulations on Omar and Feng! — Dec 26, 2019 2:48:20 AM
Congratulations on Jiangbin for his research awards! — Dec 26, 2019 2:46:30 AM
Welcome to Darren Khor! — Dec 26, 2019 2:39:42 AM
A new review paper and two collaborative papers come out! — Dec 25, 2019 3:50:50 PM
Congratulations on Jiangbin's AHA fellowship! — Dec 25, 2019 3:48:40 PM
Peng received Junior Faculty Award from BCVS2019 — Dec 25, 2019 3:45:07 PM
New paper recently published in BBRC — Aug 5, 2019 12:20:09 AM
Congratulations on Omar's T32 fellowship! — Aug 5, 2019 12:16:26 AM
Welcome Feng and Omar to join the lab — Jun 24, 2018 3:00:46 PM
Yao laboratory is open on September 1st, 2016 — Dec 6, 2017 5:47:23 AM
Matthew joined us as intern student from UofR with his major in molecular genetics and English!
Meet the first author from Circulation Research journal:
https://www.ahajournals.org/doi/full/10.1161/RES.0000000000000436
Dr Jiangbin Wu earned his BS in Bioengineering from Xi’an Jiaotong University, China and completed his PhD at Tsinghua University, China under the mentorship of Dr Yaou Zhang, where he investigated the regulatory functions of miRNAs in cancer cell cycle regulation. Because of its great impact of cardiovascular disease in human health, he joined Dr Peng Yao’s laboratory in 2016 at Aab Cardiovascular Research Institute of University of Rochester Medical School as a postdoctoral fellow, where he focused on understanding the translational regulation during cardiac fibrosis. Outside of research, he enjoys reading, watching anime, and going outside for hiking.
