Areas of Research
Our laboratory aims to understand how heart and brown adipose tissues grow during normal developmental phases and different disease conditions. Hippo-YAP pathway is a newly discovered signaling pathway that controls organ growth, which is composed of upstream kinases and downstream transcriptional regulators. Environmental signals, such as cell contact, lipid and hormones, affect the activities of the Hippo-YAP pathway kinases, which relay the signals to their transcriptional effectors to change gene expression. We are particularly interested in defining the roles of the Hippo-YAP pathway transcriptional effectors during postnatal growth. We mainly use mouse models to carry out our studies.
Using newly generated conditional knock-out mouse models, we are deciphering the crucial molecular mechanism controlling heart and brown adipose tissue growth. Investigating the molecular mechanism of how the extrinsic developmental signals control heart and brown adipose tissue growth after birth will help us understand how these two organs grow and mature. The newly discovered knowledge will pave ways for making mature human-induced pluripotent stem cell (hiPS)-derived cardiomyocytes, the available of which is a critical step for cardiac regenerative medicine. Brown adipose tissue controls the non-shivering heart generation in our body. In human, newborn babies have abundant functional brown adipose tissue, which decreases with age and almost undetectable in adult human beings. Understanding how the brown adipose tissue grows and diminishes with age will help developing new drugs treating obesity.
Except for carrying on basic research, we are also using adenovirus-associated virus (AAV) based gene therapy method to manipulate gene expression in the heart and brown adipose tissue, aiming to mitigate the disease progression, such as heart failure and obesity.
Assistant professor, Masonic Medical Research Institute
Email : firstname.lastname@example.org, Phone : 315-624-7491
I got my Ph.D from Peking University in 2008. During my Ph.D training, I worked on Arabidopsis, a plant model organism, focusing on studying the development of shoot apical meristem (SAM). After graduation, I diverted my study from plant molecular biology to cardiovascular research, and worked in the Institute of Zoology for two years. In 2009, I moved to Boston Children’s Hospital and joined in William T. Pu’s lab. In 2013, I was appointed as instructor and started building up my own research projects. In the beginning of 2018, I was recruited to MMRI to start my own lab. I am interested in deciphering mechanisms regulating heart and brown adipose tissue growth, majorly focusing on Hippo-YAP pathway. Except for doing basic research, I am also interested in doing translational research. For example, we use adeno-associated virus (AAV) or modified RNA (modRNA) as gene delivery vehicles to do gene therapy. The long goal of my lab is to first understand the basic molecular mechanism controlling heart or brown adipose tissue growth, and then apply the newly developed knowledge for developing novel therapeutic reagents targeting heart disease or obesity.
Regulation of cardiac hypertrophy remodeling.
Cardiac hypertrophic remodeling is an adaptive response of the heart to injury or pressure overload. It is beneficial at the beginning to maintain the heart function, but is detrimental in the long run. Calcineurin-NFAT pathway is a major pathway mediating pathological cardiac hypertrophic remodeling. My postdoc studies indentified miR-23a as a crucial factor regulating Calcineurin-NFAT pathway signal. My data showed that miR-23a is a direct target of NFAT. Transgenic overexpression of miR-23a predisposed the mice to β-adrenergic agonist or pressure overload induced cardiac hypertrophy. miR-23a functions by suppressing MuRF1 and Foxo3a translation. Inhibiting miR-23a with its antagomir is sufficient to suppress β-adrenergic agonist induced cardiac hypertrophy both in vitro and in vivo.
Cardiac development and regeneration
The major underlying cause of heart failure is thought to be cardiomyocyte (CM) loss. We are short of therapeutic ways to either increase the number of functional CMs or reduce the loss of CMs in heart failure patients. Activation of YAP in the heart following injury significantly improved the heart function. Pik3cb is the major transcriptional target of YAP. Activation of PIK3CB partially rescued the heart failure phenotype of cardiac specific YAP knock out mice.
Mechanism of cardiomyocyte cell cycle exit during postnatal cardiac growth.
The neonatal mouse heart has a short regeneration time window (postnatal day one to day 6). During this time window, amputated cardiac apex can be completely regenerated. After P7/P8, the CM exit cell cycle, and the heart cannot be regenerated anymore. It is already known that the cell cycle machinery is shut down after the first week of life, but the mechanism remains unknown. Our YAP study suggests that YAP/TEAD complex is essential for CM proliferation. Vestigial like 4 (VGLL4) is a suppressor of YAP/TEAD complex. In our recent study, we found that precocious activation of VGLL4 caused cardiac hypoplasia. Our data suggest that the age-related VGLL4 expression and activity regulation is crucial for neonatal heart growth. The complex balance between YAP/TEAD and VGLL4/TEAD may control the CM cell cycle exit.
- 2009, Eastwin Life Sciences-Beihai Gofar Contribution Award, Institute of Zoology, Chinese Science Academy
- 2013, Excellent Oral presentation award on Judah Folkamn research day, Boston Children’s Hospital.
- 2015, Harvard Chinese Life Science Annual Distinguished Research Award
- 2015, AHA Louis N. and Arnold M. Katz Basic Science Research Prize for Young Investigators Finalists.
- 2016, AHA BCVS new investigator travel award, Phoenix, AZ
- 2016, AHA BCVS, Oral Abstract Presentation Award, Phoenix, AZ
Ongoing Research Support
NIH R56 HL138454-01, Zhiqiang Lin (PI) 9/1/2017-8/31/2019.
Completed Research Support
- AHA postdoc fellowship 12POST9580001, Zhiqiang Lin (PI), 1/1/2012- 12/31/2013
- PCBC "JUMP START" AWARDS, 5U01HL099997-07, Michael Terrin (PI)- 1/1/16-12/31/16
- AHA Scientist Development Grant, 15SDG25590001, Zhiqiang Lin (PI)- 07/01/2015-06/30/2018
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