The Kühn Lab

The Self Healing Heart
The Self-Healing Heart

Researchers in Pittsburgh are regenerating pediatric heart tissue, potentially leading to novel approaches for the treatment of heart failure.

Learn more from UPMC Next»

Regenerating Human Hearts

While much is understood about the mechanisms of the life-sustaining pump known as the human heart, when it is examined on the cellular and molecular level many mysteries remain. Unraveling the secrets of what makes heart muscle cells different from most others in the human body is the passion of Bernhard Kühn, MD, whose laboratory resides within the Richard King Mellon Institute for Pediatric Research. Notably, these specialized contractile cells, called cardiomyocytes, are exceptional in that they lack the ability to replicate and proliferate, processes that are necessary to repair tissue damage and restore normal function.

Our innovative work has already provided insight into the growth mechanisms of these cells. The Kühn Lab’s long-term goal is to regenerate human hearts. This involves developing therapies that can help the heart muscle, the myocardium, to heal itself – to recover from a heart attack, or to help it restore a congenital heart defect to normal cardiac function without requiring surgery.

As part of the Institute for Pediatric Research, the Kühn Lab coordinates with the Heart Institute of UPMC Children’s Hospital of Pittsburgh and the McGowan Institute for Regenerative Medicine to advance its work from the research lab to clinical care.

Through its initiatives, the Kühn Lab addresses these important biological questions:

  • How do cardiomyocytes stop dividing?
  • How do differentiated cardiomyocytes re-enter the cell division cycle?
  • If cardiomyocyte regeneration can be stimulated, how can this be controlled? The answers may ultimately lead to regenerative therapies for heart failure.

Areas of Focus

The Kühn Lab within the Richard King Mellon Institute for Pediatric Research conducts cutting-edge investigations into the cellular and molecular mechanisms of the heart muscle in search of a cure for heart failure. The long-term objective is to provide cellular and molecular targets for therapeutic treatment of heart failure and congenital heart disease.

We know that natural cardiomyocyte proliferation is not sufficient to regenerate heart muscle defects in babies and children with congenital heart disease or in adults after a heart attack. Heart failure can be the result.

By focusing on the mechanisms of growth and regeneration of the myocardium, Dr. Kühn’s research has already led to important discoveries. His work has shown that administration of two naturally occurring peptides, periostin and neuregulin, can stimulate cardiomyocytes to proliferate and, in animals, repair myocardial defects and restore cardiac function.

Members of the Kühn Lab team are focused on three initial areas:

The Kühn Lab team are taking these findings and turning them into new and novel therapies for healing the hearts of children and adults.

Inducing Cardiomyocyte Proliferation

Inducing Cardiomyocyte ProliferationThe Kühn Lab has discovered that cell cycle re-entry and division of cardiomyocytes is induced by periostin peptide, a component of the extracellular matrix, and neuregulin 1 (NRG1), a growth factor. After experimentally inducing myocardial infarctions, we have shown that the administration of recombinant periostin peptide or NGR1 enhances cardiomyocyte cycling, reduces infarct size, and improves myocardial function. Using an animal model to mimic heart failure in babies and children, we are currently testing the therapeutic benefits of NGR1 administration.

We have demonstrated that a sub-population of differentiated cardiomyocytes has proliferative potential and responds to periostin peptide and NGR1 with cell cycle re-entry.

Mechanisms of Myocardial Growth and Regeneration

The Kühn Lab is exploring the signals that promote cardiomyocyte cell cycle entry and division. Regeneration is an important mechanism of tissue homeostasis in multicellular organisms, and the limited ability of the mammalian heart to regenerate is remarkable. Many mammalian tissues, such as blood and skin, regenerate after injury, relying on undifferentiated stem cells.

Heart tissue, like other tissues with limited regenerative capacity, is largely comprised of terminally differentiated cells. This means that they do not divide. However, some cardiomyocytes can re-enter the cell division cycle under certain conditions. For example, cardiomyocyte cell cycle activity in the region bordering a myocardial infarction increases transiently. Although this increase is not sufficient for effective regeneration, it suggests that some cardiomyocytes may proliferate in response to extracellular signals present in the infarct border zone.

The Kühn Lab is exploring the signals that promote cardiomyocyte cell cycle entry and division with the hope of identifying specific factors that can become leads for new medications

Translational Research

The Kühn Lab are currently working to characterize cardiomyocyte proliferation in children and adults with heart failure.

Stimulating cardiomyocyte proliferation with periostin peptide or with neuregulin 1 shows great potential for repairing the mammalian heart after injury due to myocardial infarction, or to repair congenital heart defects, such as hypoplastic left heart syndrome.

As a step toward this goal, researchers in the Kühn Lab are currently working to characterize cardiomyocyte proliferation in children and adults with heart failure.

We have demonstrated that cardiomyocyte proliferation contributes to heart growth in babies and children. This raises the possibility to target this process with new regenerative therapies. One of our regeneration factors, neuregulin, is currently in clinical phase 2 testing in adult heart failure patients. We do not have financial interests in the development of neuregulin as a therapy and look forward to advancing toward clinical trials in children. The significance and promise of research on cardiomyocyte regeneration for developing new heart failure therapies for babies and infants was recognized by a working group of the National Heart Lung and Blood Institute in 2013.

Lab Team & Contact Information

Principal Investigator

Bernhard Kühn, MD
Professor of Pediatrics and Director, Pediatric Institute for Heart Regeneration and Therapeutics (I-HRT)
Associate Director, Richard King Mellon Foundation Institute for Pediatric Research

Affiliated Faculty

Anita Saraf, MD, PhD
Assistant Professor, Heart Institute

Lab Team Contacts

*Please direct urgent requests to lab manager, Jody.

Niyatie Ammanamanchi, MS
Research Technician

Jocelyn (Jody) Mich-Basso, BS, MT
Lab Manager and Research Technician

Honghai Liu, PhD
Research Scientist

Yao Li, PhD
Research Scientist

Anita Bargaje
Research Technician

Cailynn Gregory
Research Technician

Clinical Research Team Contacts 

Shannon Janzef, MSN, RN, CBC
Lead Clinical Nurse Research Coordinator 

Administrative Team Contacts

Maureen Fortunato
Assistant Director, R.K. Mellon Institute for Pediatric Research

Kim Birsic
Administrative Coordinator

Contact Us

The Kühn Lab
UPMC Children’s Hospital of Pittsburgh
John G. Rangos Sr. Research Center, Suite 8127
4401 Penn Avenue
Pittsburgh, PA 15224

News, Presentations, & Achievements


Lab Activities and Achievements

Presentations at Scientific Meeting

Congratulations to our 3 poster presenters at the Children’s Research Symposium 2023

  • Yao Li, PhD: “Receptor Regulation of Cardiomyocyte Proliferation”.
  • Honghai Liu, PhD: “Sarcoplasmic reticulum remodeling reduces contractions in proliferating cardiomyocytes”
  • Anita Bargaje, PhD: “Validation and Results of a New Approach for Quantification of Cardiomyocyte Proliferation in Human Infants”
  • Congratulations to Anita Bargaje for her acceptance into Drexel Medical School


Lab Activities and Achievements

  • Congratulations to Yao Li, PhD, for earning a spot on the Pittsburgh Training Grant in Pediatric Pulmonary Medicine T32


Lab Activities and Achievements

  • Congratulations to Lu Han, PhD, for her promotion to Research Assistant Professor.
  • Congratulations to Jessie Yester, MD, PhD, for earning a spot on the Research Training Program for Pediatric Subspecialty Fellows T32 to the University of Pittsburgh.


Lab Activities and Achievements

  • Cardiology Fellow Jessie Yester, MD, won the 2019 Sang Park award. She will use it to advance heart regeneration research in our patients with congenital heart disease.


Lab Activities and Achievements

  • Dr. Bernhard Kühn was awarded the Aging Institute of UPMC Seed Grant Program for his project, “A function for B-type lamins in nuclear pore insertion impacts heart repair and regeneration.”


Lab Activities and Achievements

  • Honghai Liu, PhD, received the Children’s Research Advisory Committee grant to fund his research project, Repression of Epithelial Cell Transforming 2 Induces Binucleation of Cardiomyocytes.

Presentations at Scientific Meetings

  • Keystone Symposia and Cellular Biology - Molecular Mechanisms of Heart Development (X7), Keystone, Colo.
    • Honghai Liu, PhD, presented the poster “Repression of Epithelial Cell Transforming 2 Induces Binucleation of Cardiomyocytes.”
    • Abha Bais, PhD, and Niyatie Ammanamanchi, MS, presented the poster “A Transcriptional Map of Human Primary Single Cardiomyocytes.”
  • At the Society for Cardiovascular Magnetic Resonance, 20th Annual Scientific Sessions in Washington, D.C., Yijen Wu, PhD, presented her poster, entitled “Strain Derived from Tagging MRI Is More Sensitive Than Ejection Fraction for Detecting Functional Effects of Myocardial Regeneration.”
  • American Heart Association Fellows Research Day in Pittsburgh, Pa.
    • Krithika Rao, PhD, won the 3rd prize in Basic Science category for her poster presentation, “Ligands of G Protein-coupled Receptors Control Cell Cycle Activity in Neonatal Cardiomyocytes by Modulating Hippo Pathway Signaling.”
    • Honghai Liu, PhD, gave a platform presentation, entitled “ Expression of Epithelial Cell Transforming 2 Induces Bi- and Multi-nucleation of Cardiomyocytes in Mice and Humans.”
    • Balakrishnan Ganapathy, MS, gave a platform presentation, entitled “Strain Derived from Tagging MRI is More Sensitive than Ejection Fraction for Detecting Functional Effects of Myocardial Regeneration.”
    • Abha Bais, gave the platform presentation, “A Transcriptional Map of Human Cardiomyocyte Differentiation at the Single Cell Level.”
    • Christopher Lewarchik, PhD, presented the poster, “Cycling Cardiomyocytes Exhibit Altered Calcium Release.”
    • Niyatie Ammanamanchi, MS, presented the poster, “Lamin B2 Controls Nuclear Envelope Permeability and Can be Used to Regulate Cardiomyocyte Regeneration.”


Presentations at Scientific Meetings

  • Abha Bais, PhD, and Niyatie Ammanamanchi, MS, presented the poster, “ Transcriptional Map of Human Cardiomyocyte Differentiation at the Single-cell Level,” at the American Heart Association Scientific Sessions in New Orleans.
  • Rangos Research Symposium
    • Balakrishnan Ganapathy, MS, gave a platform presentation about the molecular mechanisms by which cardiomyocytes proliferate using RNA-Seq-based single cell transcriptional analysis.
    • Niyatie Ammanamanchi, MS, presented a poster detailing her results from human RNA-seq based single cell transcriptional analysis.
    • Honghai Liu, PhD, presented his poster about the cellular and molecular mechanisms by which cardiomyocytes binucleate.
  • Honghai Liu, PhD, gave a platform presentation about the cellular and molecular mechanisms by which cardiomyocytes binucleate at the Weinstein Conference in North Carolina.


News and Announcements

Lab Activities and Achievements

  • Honghai Liu, PhD, named finalist for best presentation at Fellows' Research Day, Rangos Research Center.
  • Bernhard Kühn, MD, named one of six members of a new international collaborative network funded by a 5-year grant from Fondation Leducq, to pursue heart regeneration through cardiomyocyte division.
  • Children's Hospital of Pittsburgh Foundation provided a 2-year grant, the Functional Genomics Discovery Award to Dr. Kühn for his collaborative work with Dennis Kostka, PhD.

Presentations at Scientific Meetings

  • Bernhard Kühn, MD, was an invited presenter at the American Heart Association Scientific Sessions in Orlando, Fla.
  • Bernhard Kühn, MD, made a lab research presentation at the Molecular Medicine Research Seminars, Rangos Research Center, UPMC Children's Hospital of Pittsburgh.


News and Announcements

Presentations at Scientific Meetings

  • Bernhard Kühn, MD, delivered a Grand Rounds presentation at Cincinnati Children’s Hospital.
  • Bernhard Kühn, MD, was an invited lecturer at Victor Chang Research Institute in Sydney, Australia.
  • Brian Polizzotti, PhD, gave a moderated poster presentation at the meeting of the American College of Cardiology in Washington, D.C.
  • Sangita Choudhury, PhD, received a Career Development Award from the Office of Faculty Development at Boston Children’s Hospital.
  • Bala Ganapathy, MS, presented his poster about stimulating cardiomyocyte regeneration in neonatal mice at the Basic Research Meeting of the American Heart Association in Las Vegas.


Interdependent changes of nuclear lamins, nuclear pore complexes, and ploidy regulate cellular regeneration and stress response in the heart
Yao Li, Alberto Bertozzi, Mellissa RW Mann, and Bernhard Kühn

Protocol to image and quantify nuclear pore complexes using high-resolution laser scanning confocal microscopy
Jocelyn D. Mich-Basso1 2 3, Bernhard Kühn1 2 4

Changes in nuclear pore numbers control nuclear import and stress response of mouse hearts
Han L, Mich-Basso JD, Li Y, Ammanamanchi N, Xu J, Bargaje A, Liu H, Wu L, Jeong JH, Franks J, Stolz DB, Wu YL, Rajasundaram D, Liu Y, Kühn B
Developmental Cell
2022 Oct 24

Design and rationale of a clinical trial to increase cardiomyocyte division in infants with tetralogy of Fallot
El Khoudary SR, Fabio A, Yester JW, Steinhauser ML, Christopher AB, Gyngard F, Adams PA, Morell VO, Viegas M, DaSilva J, Da Fonseca Da Silva L, Castro-Medina M, McCormick A, Reyes-Múgica M, BarlasM , Liu H, Thomas D, Ammanamanchi A, Sada R, Cuda M, Hartigan E, Groscost DK, Kühn B
International Journal of Cardiology
2021 Sep 15

Use of stable isotope-tagged thymidine and multi-isotope imaging mass spectrometry (MIMS) for quantification of human cardiomyocyte division
Yester JW, Liu H, Gyngard F, Ammanamanchi N, Little KC, Thomas D, Sullivan MLG, Lal S, Steinhauser ML & Kühn B
Nature Protocols
2021 April

Polyploid cardiomyocytes: Implications for heart regeneration
Kirillova A, Han L, Liu H, Kühn B
2021 Jul 26 

Use of stable isotope-tagged thymidine and multi-isotope imaging mass spectrometry (MIMS) for quantification of human cardiomyocyte division
Jessie W. Yester, Honghai Liu, Frank Gyngard, Niyatie Ammanamanchi, Katherine C. Little, Dawn Thomas, Mara L.G. Sullivan, Sean Lal, Matthew L. Steinhauser, and Bernhard Kühn
Nature Protocols
2021 Feb 24

Lamin B2 Levels Regulate Polyploidization of Cardiomyocyte Nuclei and Myocardial Regeneration
Lu Han, Sangita Choudhury, Jocelyn D. Mich Basso, Niyatie Ammanamanchi, Balakrishnan Ganapathy, Sangita Suresh, Mugdha Khaladkar, Jennifer Singh, Rene Maehr, Daniel A.Zuppo, Junhyong Kim, James H. Eberwine, Samuel K. Wyman, Yijen L.Wu, Bernhard Kühn
Developmental Cell
2020 April 6

Control of Cytokinesis by β-adrenergic Receptors Indicates an Approach for Regulating Cardiomyocyte Endowment
Liu H, Zhang CH, Ammanamanchi N, Suresh S, Lewarchik C, Rao K, Uys GM, Han L, Abrial M, Yimlamai D, Ganapathy B, Guillermier C, Chen N, Khaladkar M, Spaethling J, Eberwine JH, Kim J, Walsh S, Choudhury S, Little K, Francis K, Sharma M, Viegas M, Bais A, Kostka D, Ding J, Bar-Joseph Z, Wu Y, Yechoor V, Moulik M, Johnson J, Weinberg J, Reyes-Múgica M, Steinhauser ML, Kühn B
Science Translational Medicine
2019 Oct 9

Mechanisms of Cardiomyocyte Proliferation and Differentiation in Development and Regeneration
JW Yester, B Kühn
Current Cardiology Reports
2017 Feb

Neuregulin-1 Administration Protocols Sufficient for Stimulating Cardiac Regeneration in Young Mice Do Not Induce Somatic, Organ, or Neoplastic Growth
B. Ganapathy, N. Nandhagopal, B. Polizzotti, D. Bennett, A. Asan, Y. Wu, B. Kühn
2016 May 13

A cryoinjury model in neonatal mice for cardiac translational and regeneration research
BD Polizzotti, B Ganapathy, BJ Haubner, JM Penninger, B. Kühn
Nature Protocols
2016 Mar

Neuregulin stimulation of cardiomyocyte regeneration in mice and human myocardium reveals a therapeutic window (PDF)
BD Polizzotti, B Ganapathy, S Walsh, S Choudhury, N Ammanamanchi, DG Bennett, CG dos Remedios, BJ Haubner, JM Penninger, B. Kühn
Science Translational Medicine
2015 Apr 1

Cardiac regeneration based on mechanisms of cardiomyocyte proliferation and differentiation (PDF)
SE Senyo, RT Lee, B Kühn
Stem Cell Research
2014 Sep

Muscling Up the Heart - A Preadolescent Cardiomyocyte Proliferation Contributes to Heart Growth
CH Zhang, B Kühn
Circulation Research
2014 Sep 26

New mechanistic and therapeutic targets for pediatric heart failure: report from a national heart, lung, and blood institute working group (PDF)
KM Burns, BJ Byrne, BD Gelb, B Kühn, LA Leinwand, S Mital, GD Pearson, M Rodefeld, JW Rossano, BL Stauffer, MD Taylor, JA Towbin, AN Redington
2014 Jul 1

Signalling between microvascular endothelium and cardiomyocytes through neuregulin (PDF)
EM Parodi, B Kühn
Cardiovasc Res
2014 May 1 (Epub 2014 Jan 29)

Moderate and high amounts of tamoxifen in α-MHC-MerCreMer mice induce a DNA damage response, leading to heart failure and death (PDF)
K Bersell, S Choudhury, M Mollova, BD Polizzotti, B Ganapathy, S Walsh, B Wadugu, S Arab, B Kühn
Disease Models & Mech
2013 Nov (posted online 2013 Aug 7)

Cardiomyocyte proliferation contributes to heart growth in young humans (PDF) 
M Mollova, K Bersell, S Walsh, J Savla, LT Das, SY Park, LE Silberstein, CG Dos Remedios, D Graham, S Colan, B Kühn
2013 Jan 22

Intrapericardial delivery of gelfoam enables the targeted delivery of periostin peptide after myocardial infarction by inducing fibrin clot formation (PDF) 
BD Polizzotti, S Arab, B Kühn
2012 May 10

The role of neuregulin/ErbB2/ErbB4 signaling in the heart with special focus on effects on cardiomyocyte proliferation (PDF) 
B Wadugu, B Kühn B
Am J Physiol Heart Circ Physiol
2012 Mar 16

Opportunities to Join

We’d Like to Hear From You!

The Kühn Lab is always looking for talented, curious, and driven researchers to join our team.

Research Scientist

The Kuhn lab is seeking a qualified candidate for a Research Scientist position. The primary role in the laboratory will be to design, conduct, and analyze studies with a focus on cardiac regeneration. The studies will explore the terminal differentiation of heart muscle cells. The incumbent will be an active collaborator with the lab Research Director and the Principal Investigator in the development and implementation of this research and will facilitate and coordinate all aspects of this project.

Specific duties include developing and testing proposed methodologies and experimental protocols. Additionally, this individual will be expected to apply microscopy methods of the lab, as well as, be responsible for cardiomyocyte culture methods and mammalian specimen genetics. Experience in molecular biology, biochemistry, or cellular immunology is preferred.

This position is located at UPMC Children’s Hospital of Pittsburgh in Lawrenceville.

PA Child Abuse History Clearance, PA State Police Criminal Record Check, and FBI Criminal Record Check will be required prior to the start of employment. Also, a current TB test will be required as a condition of employment. EEO/AA/M/F/Vets/Disabled.

Doctoral degree (or professional degree/specialized technical training) required with 3-5 years of research experience in a related field of study. Experience in molecular biology, biochemistry, or cellular immunology is preferred.  

Graduate Students

We welcome graduate students for rotations and to do their research thesis. We are looking for applicants with previous wet-lab experience. Although we do not offer thesis projects that are purely theoretical, students with interest and background in bioinformatics, computational biology, or mathematics are encouraged to apply.

Undergraduate Students

We welcome undergraduate students from all departments and encourage first- and second-year students who are interested in a thesis project to contact us. Undergraduate students will be encouraged to stay with our lab until their graduation in order to accomplish a research project. The expected time commitment during the academic year is 10-15 hours per week, ideally in blocks of more than 3-5 hours at a time.

For inquiries regarding available positions, please contact Dr. Kühn via email.