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Jean F. Jasmin, PhD

Contact Dr. Jasmin

232 South Tenth Street
Bluemle Life Sciences Building, Rm 939
Philadelphia, PA 19107

(215) 503-9288
(215) 923-1098 fax

Medical School

PhD, University of Montreal (Montreal, Canada), Physiology - 2004

Fellowship

Post-Doctoral Fellow, Thomas Jefferson University (Philadelphia, PA), Department of Cancer Biology
Post-Doctoral Fellow, Albert Einstein College of Medicine (Bronx, NY), Department of Molecular Pharmacology

Research and Clinical Interests

CAVEOLIN-MIMETIC PEPTIDES FOR THE TREATMENT OF PULMONARY HYPERTENSION:

We and others previously reported a reduction of pulmonary Caveolin-1 expression in animal models of pulmonary arterial hypertension (PAH, WHO group I). Importantly, these reports are relevant to human PAH as decreases in Caveolin-1 expression have also been reported in patients with severe PAH. Interestingly, we recently demonstrated that short-term administration of a Caveolin-1-mimetic peptide prevented the development of monocrotaline-induced PAH and right ventricular hypertrophy in rats (Jasmin JF, Circulation 2006). However, since PAH is usually diagnosed once it is well established, it is crucial to develop new therapeutic strategies that can slow, halt and/or reverse the development of this deadly disease. Whether late administration of a Caveolin-1-mimetic peptide could reverse the development of PAH and improve survival still remains unknown. Therefore, we now plan to determine the effect of a cell-permeable Caveolin-1-mimetic peptide on the regression of PAH and right ventricular hypertrophy. For this purpose, we will use monocrotaline rats subjected to a left pneumonectomy as a reproducible animal model of severe human PAH. In addition, we are currently investigating the therapeutic potential of Caveolin-mimetic peptides on other types of pulmonary hypertension such as pulmonary hypertension associated with left heart diseases (WHO group II) and pulmonary hypertension associated with hypoxemia (WHO group III). These essential pre-clinical studies could allow the development of new therapeutic strategies for pulmonary hypertension and, consequently, have a direct impact on the management of human pulmonary hypertension.

ROLE OF CAVEOLIN PROTEINS IN MYOCARDIAL ISCHEMIC INJURIES:

Our recent findings suggest that Caveolin-1 is also involved in the pathogenesis of myocardial ischemic injury. Indeed, we recently reported that ablation of the Caveolin-1 gene exacerbated cardiac dysfunction and reduced survival in mice subjected to myocardial infarction (Jasmin JF, AJP Heart Circ Physiol, 2011). In fact, despite similar infarct sizes, Caveolin-1 KO mice subjected to a permanent left anterior descending coronary artery ligation showed reduced survival, decreased left ventricular (LV) ejection fraction and fractional shortening as well as increased LV end-diastolic pressures as compared with their WT counterparts. Mechanistically, hearts of Caveolin-1 KO mice subjected to myocardial infarction exhibited reduced beta-adrenergic receptor density at the plasma membrane as well as decreased cAMP levels and protein kinase-A phosphorylation. Collectively, our results suggest that Caveolin-1 might act as a chaperone or scaffolding protein that spatially and temporally facilitates the interactions of the different members of the beta-adrenergic signaling pathway. Accordingly, caveolar domains have previously been shown to compartmentalize several molecules involved in beta-adrenergic signaling, such as beta-adrenergic receptors, G±s, adenylate cyclase, cAMP, and protein kinase-A. We now plan to extend these findings and dissect the role of Caveolin-1 in the regulation of cardiac beta-adrenergic signaling. We also plan to evaluate the effect of Caveolin-mimetic peptides on cardiac beta-adrenergic signaling and the development of myocardial ischemic injury in both in vitro and in vivo settings. These experiments could identify new regulators of the cardiac beta-adrenergic signaling pathway. In addition, Caveolin-based therapies may become efficient alternatives for the treatment of ischemic heart diseases.

ROLE OF CAPER IN CANCER INITIATION AND PROGRESSION:

CAPER is a novel co-activator of the activator protein-1 (AP-1) and estrogen receptors that couples transcription with pre-mRNA processing. Interestingly, we recently reported increased expression of CAPER in human breast cancer specimens (Mercier I, Am J Pathol, 2009). Indeed, we demonstrated that CAPER was undetectable or expressed at relatively low levels in normal breast tissue and assumed a cytoplasmic distribution. In contrast, CAPER was expressed at higher levels in ductal carcinoma in situ and invasive ductal carcinoma specimens, where it assumed a predominantly nuclear distribution. However, the role of CAPER in breast cancer pathogenesis still remains elusive. Thus, we are currently investigating the expression of CAPER in human breast cancer specimens as well as its correlation with other biomarkers (e.g. ER, PR, HER2) and patient progression, survival and recurrence data. We will assess the possible use of CAPER as a prognostic and predictive biomarker for human breast cancer progression. In addition, we are now investigating the functional role of CAPER in breast cancer onset and progression using xenograft mouse models.