BIOPARK 1 N4E40
Undergraduate Degree: B.A. Biology, the College of the Holy Cross, 1997
Graduate Degree: M.D., University of Massachusetts Medical School, 2001
Postdoctoral Fellowship: Harvard Institute of Medicine, 2003-2005
Residency: Beth Israel Deaconess Medical Center, 2001-2008
Fellowship: University of California, San Francisco, 2008-2010
Dr. Monahan is a practicing vascular surgeon with an interest in clinically relevant vascular biology. Dr. Monahan graduated from the University of Massachusetts Medical School in 2001. While pursuing his medical degree, he began research in cardiovascular physiology. Upon completion of his degree, he trained in general surgery at the Beth Israel Deaconess Medical Center in Boston, Massachusetts. He interrupted his clinical training for two years for a post-doctoral fellowship. It was during this time that he began some of the work on which his lab now focuses. After completion of general surgery residency, He matriculated to the University of California, San Francisco for a vascular surgery fellowship. During this fellowship, he honed his research questions and began to make the framework for future grant applications. He came to the Baltimore VAMC and the University of Maryland in 2010. He has been funded by grants through the Department of Veterans Affairs, the MiMedx Corporation, and the Vascular Cures Foundation, and the National Institutes of Health.
Cardiovascular disease is a leading cause of morbidity and mortality. In the United States alone, 81 million people have cardiovascular disease which results in over 7 million revascularization procedures each year. Procedures to open blocked or occluded arteries, whether open surgical reconstruction or minimally invasive angioplasty and stenting initiate a cascade of biological events in the treated vessel. The endothelium is disrupted or denuded. The normally quiescent vascular smooth muscle cells de-differentiate and affect a migratory, proliferative, and secretory phenotype. These events lead to the formation of a lesion within the blood vessel referred to as intimal hyperplasia that ultimately limits the durability of these interventions. Dr. Monahan’s laboratory is working to develop strategies to limit or prevent intimal hyperplasia formation through selectively inhibiting vascular smooth muscle proliferation, promoting reendothelialization, and delivering therapeutic agents directly to the vessel wall in a manner consistent with current surgical practices.
Dr. Monahan used microarray analysis of canine bypass specimens to identify potential targets for therapy to prevent or limit vascular smooth muscle cell migration and proliferation. One protein that was upregulated is the myristoylated alanine-rich C kinase substrate (MARCKS). When MARCKS is silenced, VSMC proliferation is arrested, however MARCKS depletion has no effect on endothelial cell (EC) proliferation. The differential effect of MARCKS on VSMCs and ECs makes MARCKS an attractive candidate to prevent the formation of intimal hyperplasia formation. Further work has demonstrated that this differential effect on proliferation is mediated by a p27kip1-dependent mechanism. Currently his laboratory is working on defining the mechanism of regulation using techniques such as FRET imaging. Interestingly, MARCKS depletion in ECs results in increased endothelial cell migration in vitroand more rapid endothelial recovery after injury in vivo. Decreasing time to reendothelization would meet a large unmet clinical need in a variety of pathological states.
For MARCKS to be an effective therapeutic target, agents to block MARCKS signaling need to be delivered to the target tissue. Dr. Monahan has been developing siRNA-based strategies to knockdown MARCKS. Currently his laboratory is collaborating with the Department of Bioengineering at the University of Maryland, College Park to develop an siRNA-eluting stent that can deliver a controlled sustained dose of MARCKS siRNA to the vessel wall.
intimal hyperplasia, in-stent restenosis, MARCKS, p27kip1, KIS, vascular smooth muscle cell, endothelial cell
Monahan TS,Andersen ND, Martin MC, Malek JY, Shrikhande GV, Pradhan L, Ferran C, and LoGerfo FW. MARCKS silencing differentially affects human vascular smooth muscle and endothelial cell phenotypes to inhibit neointimal hyperplasia in saphenous vein. FASEB Journal.2009 Feb;23(2):557-64. PMID 18940893.
Andersen ND, Chopra A, Monahan TS, Malek JY, Jain M, Pradhan L, Ferran C, and LoGerfo FW. Endothelial cells are susceptible to rapid siRNA transfection and gene silencing ex vivo. Journal of Vascular Surgery.2010 Dec;52(6):1608-15. PMID: 20801607.
Yu D, Makkar G, Strickland DK, Blanpied T, Stumpo DJ, Blackshear PJ, Sarkar R, and Monahan TS. Myristolated Alanine-Rich Protein Kinase C Substrate (MARCKS) Regulates Small GTPase Rac1 and Cdc42 Activity and is a Critical Mediator of Vascular Smooth Muscle Cell Migration in Intimal Hyperplasia Formation. Journal of the American Heart Association.2015 Oct 8;4(10). Pii: e002255. PMID: 26450120.
Yu D, Makkar G, Dong T, Strickland DK, Sarkar R, and Monahan TS. MARCKS Signaling Differentially Regulates Vascular Smooth Muscle and Endothelial Cell Proliferation through a KIS-, p27kip1-Dependent Mechanism. PLoS One.2015 Nov3;10(11): e0141397. PMID: 26528715.
Yu D, Drucker C, Sarkar R, Ucuzian A, and Monahan TS. The Myristolated Alanine-Rich C Kinase Substrate (MARCKS) Differentially Regulates the Kinase Interacting with Stathmin (KIS) in Vascular Smooth Muscle and Endothelial Cells and Potentiates Intimal Hyperplasia Formation. Journal of Vascular Surgery. Accepted October 2018.
Farivar B, Toursavadkohi S, Monahan TS, Sharma J, Ucuzian A, Kundi R, and Lal BK. (2018) Prospective Study of Cryopreserved Placental Tissue Wound Matrix in the Management of Chronic Venous Leg Ulcers. Journal of Vascular Surgery: Venous and Lymphatic Disorders. In press2018.
Talaie T, Hansraj N, Werter C, Nagersheth K, Monahan TS, and Toursavadkohi S. (2018) Surgical scarring after arterial bypassing, an etiology of venous hypertension. Annals of Vascular Surgery. Pii: S0890-5096(18). PMID: 29886209.
Hao S, Cox S, Monahan TS, Flohr T, and Sarkar R. (2017) A defined protocol to resolving cannulation failure during endovenous ablation procedures. Annals of Vascular Surgery. 45:324-329. PMID: 28739473.
Zhang T, Azimzadeh A, Sun W, O’Neill N, Sievert E, Bergbower E, Braileanu G, Burdorf L, Cheng X, Monahan T, Dahi S, Harris D, Rybak E, Welty E, Kronfli A, Avon C, and Pierson RN. (2017) Selective CD28 inhibition modulates alloimmunity and cardiac allograft vasculopathy in anti-CD154-treated monkeys. Transplantation. 102(3): e90-e100. PMID: 29319621
Stuhldreher JM, Toursavadkohi S, Ucuzian A, Lal BK, and Monahan TS. (2017) Common carotid artery thrombosis with recurrent cerebral emboli, treated with ligation. Journal of Vascular Surgeryin submission.
Hao S, Cox S, Monahan TS, and Sarkar R. (2017) Results of ultrasound-guided double pre-puncture technique for venous radiofrequency ablation. Journal of Vascular Surgery: Venous and Lymphatic Disorders. 5(4):507-513. PMID: 28623986.
Yu D, Makkar G, Sarkar R, Strickland DK, and Monahan TS.(2017) Murine aortic crush injury – an efficient in vivo model of smooth muscle cell proliferation and endothelial function. Journal of Visualized Experimentation. 124: doi 10.3791/55201.
Chander R, and Monahan TS(2015). Ultrasound evaluation of great saphenous vein insufficiency. Journal of Vascular Diagnostics3:25-31.
Monahan TS, Belek K, and Sarkar R. (2012) Results of radiofrequency ablation of the lesser saphenous vein in the supine position. Journal of Vascular and Endovascular Surgery46(1):40-4. PMID: 22156157.
Monahan TS. (2010) Nonrecurrent inferior laryngeal nerve. Vascular and Endovascular Surgery45(1):90-1. PMID: 21193467.
Monahan TS,Chuter TAM, Reilly LM, Rapp JH, and Hiramoto JS. (2010) Long-Term Follow-up of Neck Expansion after Endovascular Aortic Aneurysm Repair. Journal of Vascular Surgery. 52(2):303-7. PMID: 20670774.
Shrikhande GV, Scali ST, Da Silva CG, Damrauer SM, Csizmadia E, Putheti P, Matthey M, Arjoon R, Patel R, Siracuse JJ, Maccariello ER, Andersen ND, Monahan TS, Kocher O, Usheva A, Veves A, Kaczmarek A, and Christiane Ferran. (2015) O-Glycosylation Regulates Ubiquitination and Degradation of the Anti-inflammatory Protein A20 to Accelerate Atherosclerosis in Diabetic ApoE-null Mice. PLoS One. 5(12):e14240. PMID 21151899.
Monahan TS, and Owens CD. (2009) Risk factors for vein graft failure. Seminars in Vascular Surgery. 22(4):216-26. PMID: 20006801.
Monahan TS, and Schneider DB. Fenestrated and branched stent grafts for repair of complex aortic aneurysms. Seminars in Vascular Surgery.22(3):132-9. PMID: 19765522.
McIntyre TP, Monahan TS, Villegas L, Doyle J, and Jones D. (2008) Telemedicine enhances effective communication and enriches medical education. Surgical Laparoscopy Endoscopy and Percutaneous Techniques.8(1):45-48. PMID 18287982
Shrikhande GV, Hamdan AD, Monahan TS,Pomposelli FB, Scovell SS, Logerfo FW, and Schermerhorn ML. (2007) Low ejection fraction predicts shortened survival in patients undergoing infrainguinal arterial reconstruction. World Journal of Surgery. 31(12):2422-6. PMID 17952496.
Monahan TS, Andersen ND, Panossian H, Kalish JA, Contreras MA, Phaneuf MD, Shrikhande GV, Ferran CJ, and LoGerfo FW. (2007) A novel function for cadherin 11/OB-cadherin in vascular smooth muscle cells: modulation of cell migration and proliferation. Journal of Vascular Surgery. 45(3):581-9. PMID 17321345.
Andersen ND, Monahan TS, Jain M, Daniel S, Caron LD, Pradhan L, Ferran C, and LoGerfo FW. (2007) Gene silencing in human vascular cells using small interfering RNAs. Journal of the American College of Surgeons 204(3):399-408. PMID 17324773.
Monahan TS, Phaneuf MD, Contreras MA, Andersen ND, Popescu-Vladimir A, Bide MJ, Dempsey DJ, Mitchell RN, LoGerfo FW, and Hamdan AD. (2006) In vivo testing of an infection-resistant annuloplasty ring. Journal of Surgical Research. 130(1):140-5. PMID 16154148.
Phaneuf MD, Bide M, Hannel S, Platek M, Monahan TS,Contreras MA, Phaneuf T, LoGerfo FW. (2005) Development of an infection-resistant, bioactive wound dressing surface. Journal of Biomedical Materials Research.74A(4):666-676. PMID 16028237.
Monahan TS, Shrikhande GV, Pomposelli FB, Skillman JJ, Campbell DR, Scovell SD, LoGerfo FW, and Hamdan AD. (2004) Preoperative cardiac evaluation does not improve or predict perioperative or late survival in asymptomatic diabetic patients undergoing elective lower extremity arterial reconstruction. Journal of Vascular Surgery41:38-45. PMID 15696041.
Lancey R, and Monahan TS. (2003) Correlation of clinical characteristics and outcomes with an injury grading system in blunt cardiac trauma. Journal of Trauma-Injury Infection & Critical Care.54(3):509-15. PMID 12634531.
Monahan TS, Sawmiller DR, Fenton RA, Dobson JG. (2000) Adenosine A2a receptor activation increases contractility in isolated perfused hearts. American Journal of Physiology. 279: H1472-H1481. PMID 11009431
2004 Mentor, William J. von Leibig Medical Student Summer Internship
2012 Reviewer, Nebraska Research Initiative
2013 Vascular Cures, E.J. Wylie Scholar "Mechanisms for differential proliferation of vascular smooth muscle and endothelial
2015 Spring: Study Section - Vascular Wall Biology Basic Science 3, The American Heart Association.
2015 Fall: Study Section - Vascular Wall Biology Basic Science 3, The American Heart Association.
2016 Spring: Study Section - Vascular Wall Biology Basic Science 3, The American Heart Association.
2016 Vascular Cures Research Summit
2017 Harvard Longwood Visiting Professor in Vascular Surgery Research
2018 Vascular Cures Research Summit
The effect of myristolated alanine-rich C kinase substrate (MARCKS) on kinase interacting with stathmin (KIS) in differential proliferation of vascular smooth muscle and endothelial cells. The objectives of this grant are to test the hypothesis that 1) MARCKS differentially regulates VSMC proliferation by regulating KIS protein abundance through ubiquitination and that that regulation and 2) that regulation is mediated through a MARCKS-KIS binding interaction and 3) that effect persists in vivoin a cell-type specific (conditional) knockout mouse.
NCT 01756833 (Site Principal Investigator)
Non-invasive treatment of abdominal aortic aneurysm clinical trial. The objective of this grant is to test the hypothesis that the MMP-inhibiting properties of doxycycline cause a decrease in abdominal aortic aneurysm growth.
Patent Number US 8,119,400 B2Monahan TS, Andersen ND, and LoGerfo FW. Methods of inhibiting vascular smooth muscle cell migration and proliferation.