Ph.D. Bioengineering , University of Pennsylvania, December 2015

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Ph.D. Bioengineering , University of Pennsylvania, December 2015

BRIANNE K. CONNIZZO, Ph.D. NIH NRSA Postdoctoral Fellow 77 Massachusetts Avenue, NE47-390 // Cambridge, MA 02139 [email protected] // 617-253-2469

EDUCATION Ph.D. Bioengineering, University of Pennsylvania, December 2015 “The Connection of Composition, Structure, and Dynamic Processes to Tendon Mechanics: Structure-Function Relationships in Collagen V Deficient Tendons” Thesis Advisor: Louis J. Soslowsky, PhD

B.S. Engineering, Smith College, May 2010 Magna Cum Laude with Highest Honors in Engineering “Compositional and Structural Effects of Myostatin Deficiency on Knockout Mice Achilles Tendons”’ Thesis Advisor: Borjana Mikic, PhD

RESEARCH EXPERIENCE Postdoctoral Research, Biological Engineering’s Continuum Electromechanics Laboratory Massachusetts Institute of Technology, Cambridge, MA, January 2016 – Present Advisor: Alan J. Grodzinsky  Developed methods to characterize the macroscale compressive mechanical properties and the nanoscale flow-dependent poroelastic properties of murine, bovine, and human tendons  Explored fluid transport in bovine and murine tendon with specific interest in developing a carrier molecule for tendon drug delivery  Investigated the development of a tendon-only and bone-tendon-muscle explant culture system for understanding the biological and mechanical etiology/progression of tendinopathy in vitro

Graduate Research, McKay Orthopaedic Research Laboratory University of Pennsylvania, Philadelphia, PA, August 2010 – December 2015 Advisor: Louis J. Soslowsky  Investigated the role of dynamic collagen I structural re-organizations in the tendon mechanical response in a variety of model systems, such as injury, disease, development, aging  Developed a novel AFM-based imaging method to measure instantaneous collagen fibril sliding and deformation in mouse tendons  Evaluated the effect of systemic ibuprofen administration in the rat rotator cuff injury model  Aided in the development of new mechanical testing protocol for mouse cervix

Undergraduate Research, Mikic Laboratory Smith College, Northampton, MA, September 2009 – May 2010 Advisor: Borjana Mikic  Explored the role of myostatin deficiency in Achilles tendon mechanics  Built mechanical testing fixtures for submerged testing of biological tissues in simulated body fluid

FUNDING 2016.2019 National Institute of Health (NIH), National Institute of Aging (NIA) NRSA F32 (Postdoctoral Fellowship Award), AG052284 “The Role of Aging in the Progression of Tendon Degeneration Due to Compressive Mechanical Overload: A Multiscale Approach”

RESEARCH INTERESTS  Cell and Tissue Mechanics o Influence of mechanical stresses on connective tissue metabolism, growth, and pathology

1 o Dynamic re-organizations in collagenous soft tissues in response to load o Nanomechanics of biological tissues and matrix proteins o Fluid flow and dynamic mechanical behavior in biological tissues  Tendon Injury, Disease and Repair o Relationship of mechanical over- and under-stimulation to tendon injury/disease o Regulation of tendon and ligament repair by extracellular matrix proteins and cells o Tendon repair augmentation via natural and synthetic materials o Biological and mechanical etiology and progression of age-related tendinopathy  Mechanobiology o Mechanical regulation of gene expression, cellular synthesis, and inflammation o Biological and mechanical regulation of assembly and degradation of extracellular matrix o Explant culture and engineered microenvironments to mimic in vivo scenarios of disease for basic science and evaluation of therapeutic interventions o Biological and functional communication across tissue types during development, maturation, and aging

HONORS AND AWARDS June 2015 PhD Competition Finalist, Characterization of Tissue Mechanics, SB3C 2015 Nov. 2014 2nd Place Biomechanics, Penn Center for Musculoskeletal Disorders Symposium June 2014 Best Poster in University of Pennsylvania Orthopaedic Annual Research Day Nov. 2013 2nd Place Biomechanics, Penn Center for Musculoskeletal Disorders Symposium June 2013 Best Poster in University of Pennsylvania Orthopaedic Annual Research Day November 2012 1st Place Biomechanics, Penn Center for Musculoskeletal Disorders Symposium June 2012 MS Competition Best Paper, Solids, Imaging and Orthopaedics, ASME SBC January 2012 2nd Place Poster, Penn Bioengineering Annual Symposium

PROFESSIONAL SERVICE AND POSITIONS 2017-present ORS Tendon Section Membership Committee 2018 Co-Chair of Gordon Research Seminar: Musculoskeletal Biology and Bioengineering 2016-present Orthopaedic Research Society Associate Member 2015-present ASME Student Member 2010 Sigma Xi, Phi Beta Kappa 2009 Tau Beta Pi

REVIEWER FOR JOURNALS Journal of the Mechanical Behavior of Biomedical Materials Plos One Journal of Biomechanics Journal of Orthopaedic Research Tissue Engineering

MENTORSHIP Name Current Position Elizabeth Feeney Ph.D. Candidate (Cornell University) Meagan Ita Ph.D. Candidate (University of Pennsylvania) Carrie Barnum Research Assistant (University of Pennsylvania) Nathan Varady Medical Student (Harvard University) Hannah Zlotnick Ph.D. Candidate (University of Pennsylvania) John Drago Medical Student (Harvard University) Cecillia Padilla Undergraduate Student (MIT)

TEACHING EXPERIENCE 2017 Educational Technology Certificate Program 2 Massachusetts Institute of Technology, Cambridge, MA 2017 Course Development, IAP Seminar on Musculoskeletal Injury and Disease Massachusetts Institute of Technology, Cambridge, MA 2016 Kaufman Teaching Certificate Program Massachusetts Institute of Technology, Cambridge, MA 2014 Teaching Assistant, BE510: Continuum Biomechanics (Graduate Level) University of Pennsylvania, Philadelphia, PA 2013 Teaching Assistant, BE455: Continuum Biomechanics (Undergraduate Level) University of Pennsylvania, Philadelphia, PA 2011-2012 Teaching Assistant, BE200: Introduction to Biomechanics (Includes Recitation) University of Pennsylvania, Philadelphia, PA 2010 Master Tutor, EGR272: Science and Mechanics of Materials Smith College, Northampton, MA, Spring 2010

OUTREACH July 2017 Women in Technology Program Biomechanics Demo Massachusetts Institute of Technology December 2016 Tendon Research Demo for Dana Hall School Massachusetts Institute of Technology February 2014 Junior BETA Day (Bioengineering Demos for 8-11 Graders from Local Schools) University of Pennsylvania May 2013 iPraxis Biomechanics Presentation for 8th Grade Class Northwood Academy Charter School May 2012 iPraxis Biomechanics Presentation for 8th Grade Class Northwood Academy Charter School

PUBLICATIONS Refereed Journal Articles Connizzo BK, Drago JM, Padilla C, Grodzinsky AJ. Bone and Muscle Degradation Impact Tendon Viability in a Murine Rotator Cuff Explant Organ Culture Model. (In Preparation) Connizzo BK, Grodzinsky AJ. Multiscale Poroviscoelastic Compressive Properties of Mouse Supraspinatus Tendons Are Altered in Young and Aged Mice. (In Review at Journal of Biomechanical Engineering) Oftadeh R*, Connizzo BK, Nia HT, Ortiz C, Grodzinsky AJ. Poroviscoelasticity of Biological Connective Tissues at the Nanoscale: Application to Tendon and Skin Biophysics. (In Preparation) Barnum CE, Fey JL, Connizzo BK, Shetye SS, Elovitz MA, Soslowsky LJ. Tensile Mechanical Properties and Dynamic Collagen Fiber Re-Alignment of the Murine Cervix are Dramatically Altered Throughout Pregnancy. J Biomech Eng. 2017: 139(6). Johnston JM, Connizzo BK, Shetye SS, Robinson KA, Huegel J, Rodriguez AB, Sun M, Adams SM, Birk DE, Soslowsky LJ. Collagen V Haploinsufficiency in a Murine Model of Classic Ehlers-Danlos Syndrome is Associated with Deficient Structural and Mechanical Healing in Tendons. J Orthop Res. 2017. Connizzo BK, Grodzinsky AJ. Tendon Exhibits Complex Poroelastic Behavior at the Nanoscale as Revealed by High-Frequency AFM-Based Rheology. J Biomech, 54:11-18. Connizzo BK, Adams SM, Adams TH, Birk DE, Soslowsky LJ. Collagen V Expression is Crucial for Regional Development of Supraspinatus Tendon. J Orthop Res. 2016: 34(12):2154-2161. Connizzo BK, Adams SM, Adams TH, Jawad AF, Birk DE, Soslowsky LJ. Multiscale Regression Modeling in Mouse Supraspinatus Tendons Reveals That Dynamic Processes Act as Mediators in Structure-Function Relationships. J Biomech 2016: S0021-9290(16):30414-6. Connizzo BK, Han L, Birk DE, Soslowsky LJ. Collagen V-Heterozygous and -Null Supraspinatus Tendons Exhibit Altered Dynamic Mechanical Behavior at Multiple Hierarchical Scales. Interface Focus 2016: 6(1):20150043. Tucker JJ, Riggin CN, Connizzo BK, Mauck RL, Steinberg DR, Kuntz AF, Soslowsky LJ, Bernstein J. Effect of Overuse-Induced Tendinopathy on Tendon Healing in a Rat Supraspinatus Repair Model. J Orthop Res. 2016: 34(1):161-6.

3 Ahmadzadeh H, Freedman BR, Connizzo BK, Soslowsky LJ, Shenoy VB. Micromechanical poroelastic finite element and shear-lag models of tendon predict large strain dependent Poisson's ratios and fluid expulsion under tensile loading. Acta Biomater. 2015: 22:83-91. Connizzo BK, Freedman BR, Fried JH, Sun M, Birk DE, Soslowsky LJ. Regulatory Role for Collagen V in Establishing the Unique Mechanical Properties of Tendons and Ligaments is Tissue-Dependent. J Orthop Res. 2015: 33(6):882-8 Sun M, Connizzo BK, Adams SM, Freedman BR, Schweitzer R, Wenstrup RJ, Soslowsky LJ, Birk DE. Targeted Deletion of Collagen V in Tendons and Ligaments Results in a Classic Ehlers-Danlos Syndrome Joint Phenotype. J Am Pathol. 2015: 185(5):1436-47. Connizzo BK, Sarver JJ, Han L, Soslowsky LJ. In Situ Fibril Stretch and Sliding is Location-Dependent in Mouse Supraspinatus Tendons. J Biomech 2014;57(16):3794-8. Connizzo BK, Bhatt PR, Liechty KW, Soslowky LJ. Diabetes Alters Mechanical Properties and Collagen Fiber Re-Alignment in Multiple Mouse Tendons. Ann Biomed Eng 2014;42(9):1880-8. Connizzo BK, Yannascoli SM, Tucker JJ, Caro AC, Riggin CN, Mauck RL, Soslowsky LJ, Steinberg DR, Bernstein J. The Detrimental Effects of Systemic Ibuprofen Delivery on Tendon Healing Are Time- Dependent. Clin Orthop Relat Res. 2014;472(8):2433-9. Ahmadzadeh H, Connizzo BK, Freedman BR, Soslowsky LJ, Shenoy VB. Determining the contribution of glycosaminoglycans to tendon mechanical properties with a modified shear-lag model. J Biomech. 2013;46(14):2497-503. Connizzo BK, Yannascoli SM, Soslowsky LJ. Structure-function relationships of postnatal tendon development: A parallel to healing. Matrix Biol. 2013;32(2):106-16. Connizzo BK, Sarver JJ, Iozzo RV, Birk DE, Soslowsky LJ. Effect of age and proteoglycan deficiency on collagen fiber re-alignment and mechanical properties in mouse supraspinatus tendon. J Biomech Eng. 2013;135(2):021019. Miller KS, Connizzo BK, Feeney E, Soslowsky LJ: Characterizing Local Collagen Fiber Re-Alignment and Crimp Behavior Throughout Mechanical Testing in a Mature Mouse Supraspinatus Tendon Model. J Biomech. 2012 Aug 9;45(12):2061-5. Miller KS, Connizzo BK, Feeney E, Tucker JJ, Soslowsky LJ: Examining differences in local Collagen Fiber Crimp Frequency Throughout Mechanical Testing in a Developmental Mouse Supraspinatus Tendon Model. J Biomech Eng. 2012 Apr;134(4):041004. Miller KS, Edelstein L, Connizzo BK, Soslowsky LJ: Effect of Preconditioning and Stress Relaxation on Local Collagen Fiber Re-Alignment: Inhomogeneous Properties of Rat Supraspinatus Tendon. J Biomech Eng. 2012 Mar;134(3):031007 Beason DP, Connizzo BK, Dourte LM, Edelstein L, Tucker JJ, Liu SS, Mauck RL, Soslowsky LJ, Steinberg DR, Bernstein J. Fiber-Aligned Polymer Scaffolds for Rotator Cuff Repair in a Rat Model. Journal of Shoulder and Elbow Surgery. 2012 Feb;21(2):245-50. Miller KS, Connizzo BK, Soslowsky LJ: Collagen Fiber Re-Alignment in a Neonatal Developmental Mouse Supraspinatus Tendon Model. Ann Biomed Eng. 2012 May;40(5):1102-10.

Conference Abstracts (* indicates podium presentation) Connizzo BK, Grodzinsky AJ. Bone and Muscle Degradation Impact Tendon Viability in a Murine Rotator Cuff Explant Organ Culture Model. (Submitted to ORS Annual Meeting 2018) Connizzo BK, Zlotnick HM, Drago JM, Grodzinsky AJ. Development and Characterization of an In Vitro Tendon-Muscle-Bone Explant Culture. (BMES Annual Meeting 2017) *Connizzo BK, Grodzinsky AJ. Aged Supraspinatus Tendons Have Altered Dynamic Compressive and Poroelastic Properties. (SB3C 2017) Connizzo BK, Grodzinsky AJ. Dynamic Compressive Mechanical Properties of Supraspinatus Tendons Are Altered in Aged Mice. 42:586, 2017. (ORS Annual Meeting 2017) *Connizzo BK, Adams SM, Adams TH, Jawad AF, Birk DE, Soslowsky LJ. Multiscale Regression Modeling in Mouse Supraspinatus Tendons Reveals Regional Contribution of Dynamic Processes to Structure-Function Relationships. Proceedings of 2016 Summer Bioengineering, Biotransport, and Biomechanics Conference, SB3C2016-030. (SB3C 2016) *Connizzo BK, Adams S, Birk DE, Soslowsky LJ. Structure and Composition in Tendons with Altered Collagen V Expression are Location-Dependent. Trans Orthop Res Soc 41:349, 2016. (ORS Annual Meeting 2016)

4 Connizzo BK, Han L, Birk DE, Soslowsky LJ. Collagen V-Deficient Tendons Exhibit Altered Dynamic Mechanical Behavior at Multiple Hierarchical Scales. Trans Orthop Res Soc 40:641, 2016. (ORS Annual Meeting 2016) *Connizzo BK, Birk DE, Soslowsky LJ. The Dynamic Mechanical Response is Severely Altered in Collagen V Deficient Mouse Supraspinatus Tendons. Proceedings of 2015 Summer Bioengineering, Biotransport, and Biomechanics Conference, SB3C2015-104. (ASME SB3C 2015, PhD Competition Finalist) *Connizzo BK, Fried JH, Sun M, Birk DE, Soslowsky LJ. Critical Regulatory Role for Collagen V in Establishing the Unique Mechanical Properties of Joint Stabilizing Tendons. Trans Orthop Res Soc 40:191, 2015. (ORS Annual Meeting 2015) Tucker JJ, Connizzo BK, Riggin CN, Mauck RL, Steinberg DR, Kuntz AF, Soslowsky LJ, Bernstein J. Tendon Healing in a Supraspinatus Tear and Repair Rat Model is not Altered by Overuse-Induced Tendinopathy. Trans Orthop Res Soc 40:1373, 2015. (ORS Annual Meeting 2015) Sun M, Connizzo BK, Adams SM, Freedman BR, Johnson R, Schweitzer R, Soslowsky LJ, Birk DE. A Tendon-Specific Collagen V-Null Mouse Model Demonstrates A Joint Phenotype Characteristic of Classic Ehlers-Danlos Syndrome. (American Society for Matrix Biology Biennial Meeting 2014) Connizzo BK, Sarver JJ, Han L, Soslowsky LJ. In Situ Fibril Stretch in Mouse Supraspinatus Tendons is Location-Dependent. (Poster Presentation (W93) at 7th World Congress of Biomechanics 2014) *Connizzo BK, Freedman BR, Sun M, Birk DE, Soslowsky LJ. Collagen V Null Mice Have Decreased ACL Mechanical Properties and Altered Fibril Morphology. Trans Orthop Res Soc 39:110, 2014. (ORS Annual Meeting 2014) Connizzo BK, Feeney E, Iozzo RV, Birk DE, Soslowsky LJ. In Situ Collagen Crimp is Altered with Age and Proteoglycan Deficiency in Mouse Supraspinatus Tendons. Trans Orthop Res Soc 39:1346, 2014. (ORS Annual Meeting 2014) Connizzo BK, Birk DE, Iozzo RV, Soslowsky LJ. Effects of Decorin and Biglycan on Re-Alignment and Mechanical Properties of Aging Supraspinatus Tendons. Trans Orthop Res Soc 38:613, 2013. (ORS Annual Meeting 2013) Connizzo BK, Liechty KW, Soslowsky LJ. Altered Mechanical Properties and Fiber Re-Alignment in db/db Mouse Supraspinatus and Achilles Tendons. Proceedings of ASME 2012 Summer Bioengineering Conference, SBC2012-80129. (ASME Summer Bioengineering Conference 2012) *Miller KS, Connizzo BK, Feeney E, Soslowsky LJ. Collagen Fiber Re-Alignment and Mechanical Properties in a Mouse Supraspinatus Tendon Model: Examining Changes with Age and Location. Proceedings of ASME 2012 Summer Bioengineering Conference, SBC2012-80129. (ASME Summer Bioengineering Conference 2012) Beason DP, Connizzo BK, Dourte LM, Edelstein L, Tucker JJ, Liu SS, Mauck RL, Soslowsky LJ, Steinberg DR, Bernstein J. Fiber-Aligned Polymer Scaffolds for Rotator Cuff Repair in a Rat Model. Trans Orthop Res Soc 37:1664, 2012. (ORS Annual Meeting 2012) Miller KS, Connizzo BK, Tucker JJ, Feeney E, Trasolini NR, Soslowsky LJ. Local Differences in Collagen Fiber Crimp Throughout Mechanical Testing in a Mouse Supraspinatus Tendon Model. Trans Orthop Res Soc 37:1290, 2012. (ORS Annual Meeting 2012) Miller KS, Connizzo BK, Tucker JJ, Soslowsky LJ. Collagen Fiber Re-Alignment in a Neonatal Developmental Mouse Supraspinatus Tendon Model. Trans Orthop Res Soc 37:1289, 2012. (ORS Annual Meeting 2012) Mikic B, Connizzo B, McGrath M, Shea J, Bierwert L: The Effect of Myostatin Deficiency on Murine Tendon Material Behavior, Trans Orthop Res Soc 36:916, 2011. (ORS Annual Meeting 2011)

PRESENTATIONS Conference Podium Presentations June 24th, 2017 Aged Supraspinatus Tendons Have Altered Dynamic Compressive and Poroelastic Properties. SB3C 2017. Tucson, AZ. July 2nd, 2016 Multiscale Regression Modeling in Mouse Supraspinatus Tendons Reveals Regional Contribution of Dynamic Processes to Structure-Function Relationships. SB3C 2016. National Harbor, MD. March 7th, 2016 Structure and Composition in Tendons with Altered Collagen V Expression are Location-Dependent. ORS 2016. Orlando, FL.

5 June 19th, 2015 The Dynamic Mechanical Response is Severely Altered in Collagen V Deficient Mouse Supraspinatus Tendons. SB3C 2015. Snowbird, UT. March 31st, 2015 Critical Regulatory Role for Collagen V in Establishing the Unique Mechanical Properties of Joint Stabilizing Tendons. ORS 2015. Las Vegas, NV. June 13th, 2014 Collagen V Null Mice Have Decreased ACL Mechanical Properties and Altered Fibril Morphology. Penn Orthopaedic Research Day. Philadelphia, PA. March 16th, 2014 Collagen V Null Mice Have Decreased ACL Mechanical Properties and Altered Fibril Morphology. ORS 2014. New Orleans, LA.

Invited Lectures/Seminars July 29th, 2016 Role of Aging in the Progression of Rotator Cuff Tendinopathy Due to Compressive Loading. Continuum Electromechanics Retreat. Dedham, MA. June 29th, 2015 Multi-scale Mechanical Evaluation of Collagen V Deficient Mouse Supraspinatus Tendons. Tufts University. Medford, MA. May 29th, 2015 Multi-scale Mechanical Evaluation of Collagen V Deficient Mouse Supraspinatus Tendons. University of California at San Diego. La Jolla, CA.

REFERENCES Alan J. Grodzinsky, ScD Professor of Biological, Electrical, and Mechanical Engineering Massachusetts Institute of Technology 77 Massachusetts Avenue, NE47-377 Cambridge, MA 02139 Email: [email protected]

Louis J. Soslowsky, PhD Fairhill Professor of Orthopaedic Surgery University of Pennsylvania 424 Stemmler Hall 34th and Hamilton Walk Philadelphia, PA 19104 Email: [email protected]

Robert L. Mauck, PhD Mary Black Ralston Professor for Education and Research in Orthopaedic Surgery University of Pennsylvania 424 Stemmler Hall 34th and Hamilton Walk Philadelphia, PA 19104 Email: [email protected]

David E. Birk, PhD Distinguished Professor of Molecular Pharmacology & Physiology Morsani College of Medicine, University of South Florida 12901 Bruce B. Downs Boulevard, MDC 8 Tampa, FL 33612 Email: [email protected]

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