The candidate's immediate career goal is to obtain an Assistant Professor position at an academic Cardiology Division that allows for protected (75%) research time with a 25% clinical obligation. Ideally, the research will be translational work aimed toward improved diagnosis and treatment of cardiovascular disease. Because the candidate is trained in advanced cardiac imaging, the opportunity to employ these imaging skills in both the clinical and investigational settings will be critical. Long-term, the candidate hopes to establish a diverse and robust research program that validates new molecular imaging targets at the bench, and then tests the utility of those targets in clinical trials. This research proposal will examine the ability of non-invasive molecular imaging to detect cell death and cardiac remodeling in vivo. Specifically, cardiac magnetic resonance (CMR), which provides superior depth penetration and spatial resolution, will be used to image magnetically-labeled Annexin V (ANX-SPIO), which has been shown to bind cells early in apoptosis. The major hypothesis is that systemically delivered ANX-SPIO will be able to track to and monitor (by MRI) areas of myocardial cell death following either myocardial infarction or cardiotoxic doxorubicin exposure. This methodology is novel in its approach, and pursuit of this critical frontier in cardiac molecular imaging may lead to a new platform from which cardiovascular disease is both studied and treated. This proposal incorporates significant career development for the candidate. Through critical interactions with a rich cohort of mentors in Cardiac MRI, molecular imaging, and cardiac apoptosis/cell biology, the candidate will obtain invaluable and broad technical training in the fields that will lay the foundation for an independent research program in cardiac molecular imaging. The research environment at UCSF is ideally suited for this endeavor. Combined with concurrent coursework in biostatistics and various molecular imaging techniques (bioluminescence, MR-SPECT), these experiences will help the candidate compete for R01 funding to establish the aforementioned independent research program.

Public Health Relevance

Using magnetic labeling to detect heart muscle damage may allow real-time adjustments to chemotherapy regimens, thereby preventing the irreversible heart failure that can result from these treatments. A similar strategy to monitor stem cell protection of threatened myocardium after heart attacks may also be possible. Thus, the ability to detect cardiac cell death through MRI may positively impact patient care and outcomes.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Clinical Investigator Award (CIA) (K08)
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Special Emphasis Panel (ZHL1-CSR-O (M1))
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Carlson, Drew E
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Stanford University
Internal Medicine/Medicine
Schools of Medicine
United States
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Dash, Rajesh; Mitsutake, Yoshiaki; Pyun, Wook Bum et al. (2018) Dose-Dependent Cardioprotection of Moderate (32°C) Versus Mild (35°C) Therapeutic Hypothermia in Porcine Acute Myocardial Infarction. JACC Cardiovasc Interv 11:195-205
Chung, Wook-Jin; Cho, Ahryon; Byun, Kyunghee et al. (2016) Apelin-13 infusion salvages the peri-infarct region to preserve cardiac function after severe myocardial injury. Int J Cardiol 222:361-367
Dash, Rajesh; Kim, Paul J; Matsuura, Yuka et al. (2015) Manganese-Enhanced Magnetic Resonance Imaging Enables In Vivo Confirmation of Peri-Infarct Restoration Following Stem Cell Therapy in a Porcine Ischemia-Reperfusion Model. J Am Heart Assoc 4:
Lin, Shin; Tremmel, Jennifer A; Yamada, Ryotaro et al. (2013) A novel stress echocardiography pattern for myocardial bridge with invasive structural and hemodynamic correlation. J Am Heart Assoc 2:e000097
Chung, Jaehoon; Dash, Rajesh; Kee, Kehkooi et al. (2012) Theranostic effect of serial manganese-enhanced magnetic resonance imaging of human embryonic stem cell derived teratoma. Magn Reson Med 68:595-9
Lam, Justin; Simpson, Paul C; Yang, Phillip C et al. (2012) Synthesis of an in vivo MRI-detectable apoptosis probe. J Vis Exp :
Kosuge, Hisanori; Sherlock, Sarah P; Kitagawa, Toshiro et al. (2012) Near infrared imaging and photothermal ablation of vascular inflammation using single-walled carbon nanotubes. J Am Heart Assoc 1:e002568
Dash, Rajesh; Chung, Jaehoon; Ikeno, Fumiaki et al. (2011) Dual manganese-enhanced and delayed gadolinium-enhanced MRI detects myocardial border zone injury in a pig ischemia-reperfusion model. Circ Cardiovasc Imaging 4:574-82
Chung, Jaehoon; Kee, Kehkooi; Barral, Joëlle K et al. (2011) In vivo molecular MRI of cell survival and teratoma formation following embryonic stem cell transplantation into the injured murine myocardium. Magn Reson Med 66:1374-81
Dash, Rajesh; Chung, Jaehoon; Chan, Trevor et al. (2011) A molecular MRI probe to detect treatment of cardiac apoptosis in vivo. Magn Reson Med 66:1152-62