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Sharlene M. Day, MD

Sharlene M. Day, MD Physician

Dr. Day is employed by Penn Medicine.

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Clinical Specialties


  • Cardiology

Programs & Centers:

Board Certification:

  • Cardiovascular Disease, 2012

Clinical Expertise:

  • Athlete's Heart
  • Cardiac Arrest
  • Cardiomyopathy
  • Dilated Cardiomyopathy
  • Familial Cardiomyopathy
  • Hypertrophic Cardiomyopathy

Practice Locations and Appointments

Insurance Accepted

  • Aetna US Healthcare
  • Amerihealth Caritas
  • Amerihealth Caritas Medicare
  • Cigna
  • Cigna HealthSpring
  • Clover Health Plan
  • CVS Health
  • Devon Health Services (Americare)
  • eLAP Services
  • Gateway Health Plan
  • Geisinger Health Plan
  • HealthAmerica / HealthAssurance, a Coventry Plan
  • HealthPartners
  • HealthPartners Medicare
  • HealthSmart
  • Highmark Blue Shield
  • Homestead Smart Health Plans
  • Horizon Blue Cross Blue Shield of New Jersey
  • Humana / Choicecare
  • Independence Blue Cross (Keystone East)
  • Intergroup
  • Keystone First
  • Keystone First Medicare
  • Multiplan
  • NJ Medicaid
  • NJ Qualcare
  • Oxford Health Plan
  • PA Health and Wellness (Centene) Medicare
  • PA Medicaid
  • PA Medicare
  • Preferred Health Care/LGH
  • Provider Partners Health Plan
  • Rail Road Medicare / Palmetto GBA
  • Remedy Partners at Penn Medicine
  • Tricare
  • United Healthcare
  • UnitedHealthcare Community Plan
  • US Family Health Plan
  • Veterans Choice Program

Education and Training

Medical School: New York University School of Medicine
Residency: University of Michigan Medical Center
Fellowship: University of Michigan Medical Center


"Provider Education and Public Awareness of Sudden Cardiac Death in the Young Risk Factors", Action team leader, Sudden Cardiac Death in the Young in Michigan: Call to Action, Lansing, MI, Local American College of Cardiology, National American College of Physicians, National American Heart Association Guideline Committee for the Diagnosis and Treatment of Hypertrophic Cardiomyopathy, National American Heart Association Writing Group for Genetic Testing for Inherited Cardiovascular Disease, National American Heart Association, National Mid-Career Investigators' Committee, International Society of Heart Research, International NIH Cardiovascular Domain Working Group for the Clinical Genome Resource (ClinGen), National NIH Myocardial Ischemia and Metabolism Study Section, National Sarnoff Cardiovascular Research Foundation Scientific Committee, National Sarnoff Cardiovascular Research Foundation Scientific Committee, National Sarnoff Foundation Nominating Committee for the Scientific Committee, National University of Michigan Cardiovascular Center McKay Grant Review Committee, Local

Hospital Affiliation

Dr. Day is employed by Penn Medicine.

Hospital Privileges:

  • Hospital of the University of Pennsylvania: Has privileges to treat patients in the hospital.


Description of Research Expertise:

My research program primarily focuses on hypertrophic cardiomyopathy (HCM), the most common genetic cardiovascular disease of Mendelian inheritance. Our research program integrates basic, translational and clinical science. We have a strong interest in learning how genetic and non-genetic factors (particularly exercise) influence the cardiovascular phenotype and clinical outcomes in patients. We have pursued these questions through a large multicenter registry and several clinical trials. To better understand the molecular pathophysiology of HCM, we leverage a variety of resources and model systems, including human heart tissue from genotyped HCM patients, exogenous expression of sarcomere gene mutations in primary cardiac myocytes, and a series of human inducible pluripotent stem cell-derived cardiac myocyte (hiPSC-CM) models of hypertrophic cardiomyopathy in isogenic lines through genome-editing, as well as patient-derived iPSC lines. Our early work focused on defining gene and allele-specific sarcomere gene expression and specific alterations in calcium homeostasis in human HCM. In recent years, we have primarily focused on myosin binding protein C (MYBPC3), the gene that harbors the largest number of mutations causal for hypertrophic cardiomyopathy. In human myocardium from patients with MYBPC3 mutations, we have defined loss-of-function, or haploinsufficiency of MYBPC3, as the primary pathophysiology. Our lab has identified a critical regulator, the HSP70 family of molecular chaperones, in the turnover of MYBPC3 and are pursuing this pathway as a possible therapeutic target. We have recently completed a small molecule screen of ~2500 compounds in patient-derived iPSC-CMs and have identified a number of other putative candidates that could restore haploinsufficiency of MYBPC3 caused by mutations in this gene.

Selected Publications:

Walsh R, Mazzarotto F, Whiffin N, Buchan R, Midwinter W, Wilk A, Li N, Felkin L, Ingold N, Govind R, Ahm, ad M, Mazaika E, Allouba M, Zhang X, de Marvao A, Day SM, Ashley E, Colan SD, Michels M, Pereira AC, Jacoby D, Ho CY, Thomson KL, Watkins H, Barton PJR, Olivotto, I, Cook SA, Ware JS.: Quantitative Approaches to Variant Classification Increase the Yield and Precision of Genetic Testing for Mendelian Diseases: The Case for Hypertrophic Cardiomyopathy. Genome Medicine 11 (article 5): 2-18,2019.

Garratt M, Leander D, Pifer K, Herrera J, Day SM, Fiehn O, Brooks S, Miller RA.: 17-alpha Estradiol Ameliorates Age-Associated Sarcopenia and Improves Late Life Physical Function in Male Mice But Not in Females or Castrated Males Aging Cell 18 (2): e12920,2019.

Day SM: Nonobstructive Hypertrophic Cardiomyopathy: The High Hanging Fruit. JAMA Cardiol 4 (3): 235-236,2019 .

Vigneault DM, Yang E, Jensen PJ, Tee MW, Farhad H, Chu L, Noble JA, Day SM, Colan SD, Russell MW, Towbin J, Sherrid MV, Canter CE, Shi L, Ho CY, Bluemke DA: Left Ventricular Strain Is Abnormal in Preclinical and Overt Hypertrophic Cardiomyopathy: Cardiac MR Feature Tracking. Radiology 290 (3): 640-48,2019.

Smith ED, Tome J, Mcgrath R, Kumar S, Concannon M, Day SM, Saberi S, Helms AS: Exercise hemodynamics in hypertrophic cardiomyopathy identify risk of incident heart failure but not ventricular arrhythmias or sudden cardiac death. Int J Cardiol 274 : 226-231,2019.

Ho C, Day SM, Ashley E, Michels M, Pereira A, Jacoby D, Lakdawala N, Ware J, Helms AS, Colan SD, Seidman CE, Olivotto I: Response to letter regarding article “Genotype and Lifetime Burden of Disease in Hypertrophic Cardiomyopathy: Results from the Sarcomeric Cardiomyopathy Registry (SHaRe) Circulation 139 (12): 1559-1560,2019.

O'Leary TS, Snyder J, Sadayappan S, Day SM, Previs MJ: MYBPC3 truncation mutations enhance actomyosin contractile mechanics in human hypertrophic cardiomyopathy. J Mol Cell Cardiol 127 : 165-173,2018.

Glazier AA, Thompson A, Day SM: Allelic imbalance and haploinsufficiency in MYBPC3-linked hypertrophic cardiomyopathy. Pflugers Arch : 1-13,2018.

Ho CY, Day, SM, Ashley EA, Michels M, Pereira A, Jacoby D, Fox J, Caleshu C, Cirino AL, Ware J, Helms AS, Colan SD, Signorovich J, Green E, Olivotto I: Genotype and Lifetime Burden of Disease in Hypertrophic Cardiomyopathy: Insights from the Sarcomeric Human Cardiomyopathy Registry (SHaRe). Circulation 138 (14): 1387-98,2018.

Ahmad F, McNally EM, Ackerman MJ, Baty LC, Day SM, Kullo IJ, Madueme PC, Maron MS, Martinez MW, Phetteplace JE, Salberg L, Taylor MR: Establishment of Specialized Clinical Cardiovascular Genetics Programs: Recognizing the Need and Meeting the Standards Circ Genom Precis Med 12 (6): 286-305,2019.

Ko C, Arscott P, Saberi S, Concannon M, Day SM, Yashar BM, Helms AS: Genetic Testing Impacts the Utility of Prospective Familial Screening in Hypertrophic Cardiomyopathy Through Identification of a Non-Familial Subgroup Genetics in Medicine 20 (1): 69-75,2018.

Reineck E, Rolston B, Bragg-Gresham JL, Salberg L, Baty L, Kumar S, Wheeler MT, Ashley E, Saberi S, Day SM: Physical activity and other health behaviors in adults with hypertrophic cardiomyopathy. Am J Cardiol 111 (7): 1034-9,2013.

Helms AS, Davis FM, Coleman D, Bartolone SN, Glazier AA, Pagani F, Yob JM, Sadayappan S, Pedersen E, Lyons R, Westfall MV, Jones R, Russell MW1, Day SM: Sarcomere mutation-specific expression patterns in human hypertrophic cardiomyopathy. Circ Cardiovasc Genet 7 (4): 434-43,2014.

Helms AS, Day SM: Hypertrophic cardiomyopathy: single gene disease or complex trait? Eur Heart J 37 (23): 1823-5,2016.

Homburger JR, Green EM, Caleshu C, Sunitha MS, Taylor RE, Ruppel KM, Metpally RPR, Colan SD, Michels M, Day SM, Olivotto I, Bustamante CD, Dewey FE, Ho Y, Spudich JA, Ashley EA: Multidimensional structure-function relationships in human β-cardiac myosin from population-scale genetic variation. PNAS 113 (24): 6701-6,2016.

Monteiro da Rocha A1, Guerrero-Serna G2, Helms A2, Luzod C2, Mironov S2, Russell M3, Jalife J2, Day SM2, Smith GD4, Herron TJ5.: Deficient cMyBP-C protein expression during cardiomyocyte differentiation underlies human hypertrophic cardiomyopathy cellular phenotypes in disease specific human ES cell derived cardiomyocytes. J Mol Cell Cardiol 99 : 197-206,2016.

Helms AS, Alvarado FJ, Yob J, Tang VT, Pagani F, Russell MW, Valdivia HH, Day SM.: Genotype-Dependent and -Independent Calcium Signaling Dysregulation in Human Hypertrophic Cardiomyopathy. Circulation 134 (22): 1738-1748,2016.

Ho CY, Day SM, Colan SD, Russell MW, Towbin JA, Sherrid MV, Canter CE, Jefferies JL, Murphy AM, Cirino AL, Abraham TP, Taylor M, Mestroni L, Bluemke DA, Jarolim P, Shi L, Sleeper LA, Seidman CE, Orav EJ; HCMNet Investigators: The Burden of Early Phenotypes and the Influence of Wall Thickness in Hypertrophic Cardiomyopathy Mutation Carriers: Findings From the HCMNet Study. JAMA Cardiol 2 (4): 419-428,2017.

Saberi S, Wheeler M, Bragg-Gresham J, Hornsby W, Agarwal PP, Attili A, Concannon M, Dries AM, Shmargad Y, Salisbury H, Kumar S, Herrera JJ, Myers J, Helms AS, Ashley EA, Day SM: Effect of Moderate-Intensity Exercise Training on Peak Oxygen Consumption in Patients With Hypertrophic Cardiomyopathy: A Randomized Clinical Trial. JAMA 317 (13): 1349-1357,2017.

Cirino AL, Harris S, Lakdawala NK, Michels M, Olivotto I, Day SM, Abrams DJ, Charron P, Caleshu C, Semsarian C, Ingles J, Rakowski H, Judge DP1, Ho CY: Role of Genetic Testing in Inherited Cardiovascular Disease: A Review. JAMA Cardiol 2 (10): 1153-1160,2017.

Furqan A, Arscott P, Girolami F, Cirino AL, Michels M, Day SM, Olivotto I, Ho CY, Ashley E, Green EM, Caleshu C, SHaRe Consortium: Care in Specialized Centers and Data Sharing Increase Agreement in Hypertrophic Cardiomyopathy Genetic Test Interpretation. Circ Cardiovasc Genet 10 (5): pii: e001700,2017.

Saberi S, Day SM: Vigorous exercise in hypertrophic cardiomyopathy: Benefits may outweigh the risks. Int J Cardiol 250 : 229-230,2018.

Saberi Sara, Day Sharlene M: Exercise and Hypertrophic Cardiomyopathy: Time for a Change of Heart. Circulation 137 (5): 419-421,2018.

Limongelli G, Bossone E, Elliott PM, Day SM: On the Road from Gene to Therapy in Inherited Cardiomyopathies. Heart Fail Clin 14 (2): xi-xv,2018.

Tang VT, Arscott P, Helms AS, Day SM: Whole-Exome Sequencing Reveals GATA4 and PTEN Mutations as a Potential Digenic Cause of Left Ventricular Noncompaction. Circ Genom Precis Med 11 (1): e001966,2018.

Glazier AA, Hafeez N, Mellacheruvu D, Basrur V, Nesvizhskii AI, Lee LM, Shao H, Tang V, Yob JM, Gestwicki JE, Helms AS, Day SM: HSC70 is a chaperone for wild-type and mutant cardiac myosin binding protein C. JCI Insight 3 (11): pii: 99319,2018.

LLee SP, Ashley EA, Homburger J, Caleshu C, Green EM, Jacoby D, Colan SD, Arteaga-Fernández E, Day SM, Girolami F, Olivotto I, Michels M, Ho CY, Perez MV, SHaRe Investigators: Incident Atrial Fibrillation Is Associated With MYH7 Sarcomeric Gene Variation in Hypertrophic Cardiomyopathy. Circ Heart Fail 11 (9): e005191,2018.

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Academic Contact Info

3400 Civic Center Blvd
Smilow 11-102

Philadelphia, MI 48109-0644
Phone: (215) 573-4650
Patient appointments: 800-789-7366 (PENN)