Rafiq Research


Name: Khadija Rafiq, PhD
Position: Assistant Professor of Medicine, Division of Cardiology
Organization: Department of Medicine

1020 Locust Street
JAH, Room 543A
Philadelphia, PA 19107

Telephone: 215-503-5593

Our research focuses on the identification and characterization of key proteins and pathways that regulate cardiac inflammation induced during pathological conditions, such as diabetes mellitus, sepsis, and cardiac injury. The lab focuses on targeting 1) B cell inflammatory gene, allograft inflammatory factor-1 (AIF-1), and 2) Mitochondrial 3‐hydroxy‐3‐methylglutaryl‐CoA (HMG‐CoA) synthase (HMGCS2), as a new therapy to limit inflammation, myocyte loss, and enhance cardiac function in heart failure related diabetes. These questions are addressed by employing in vitro models of gain- and loss-of-function of molecules of interest. In vitro findings are further supported by in vivo transgenic mice models that either selectively overexpress or delete the candidate molecules in the mouse heart.  The lab employs dynamic state-of-art technologies to dissect disease mechanism and identify potential therapeutic targets. Frequently used research approaches include proteomics, chemical, biochemical, immunological, and pathophysiological approaches. Our long-term goals are to provide novel insights about the molecular pathways that govern cardiac myocyte growth and function and to use this information to devise pharmacologic and genetic therapies for heart diseases in humans.

Research Projects

B Cells & Cardiac Repair

One prime focus in the lab is to delineate the interplay among B cell immunity, cardiac AIF-1 expression, and cardiac structural and functional changes during the development of cardiovascular disease after diabetes insults.

The ability of B cells to produce antibodies in the context of adaptive immune responses makes them an attractive target of interest. However, there is strong evidence of additional functions for mature B cells beyond antibody production. Mature B cells can be divided into two lineages based on a combination of cell surface markers and functional properties. B2 cells, which include a predominant population of follicular B cells and a smaller population of marginal zone B cells, are produced postnatally and represent the vast majority of B cells in the adult. B1 cells, which include B1a (CD5+) and B1b (CD5-) subsets, are produced mostly during prenatal life and are considered major contributors to production of “preimmune antibodies generated in the absence of exogenous antigenic stimulation. B cells can modulate both adaptive and innate immune responses, as well as play a role in the pathogenesis of a variety of human diseases. They can present antigens to T cells, produce cytokines and chemokines that ultimately modulate the function of other leukocytes. B cells can also act as negative regulators of the immune response, mostly through the production of IL-10, IL-35, and TGF-β. These B cells with anti-inflammatory properties, often referred to as B regulatory or B10 cells, are immunosuppressive cells that support immunologic tolerance and resolution of the acute inflammatory response. Given the important role that B cells play in myocardial injury, it is crucial to elucidate the biology of myocardial B cells in the development of DCM. Our long-term goals are to develop a therapy targeting AIF-1 to maintain cardiac resident B cell immune responses to attenuate cardiac inflammation and maintain cardiac function during the development of cardiovascular disease after diabetes insults. 

HMGCS2 & Heart Failure

My laboratory focuses on understanding the interrelationship between myocardial glucose and the ketogenesis rate-limiting enzyme 3-Hydroxymethylglutaryl-CoA synthase 2 (HMGCS2) during the development of cardiovascular disease after diabetes insults.

HMGCS2 translocate to mitochondria, following activation, and upregulates fatty acid oxidation yield high energy compounds which are converted to acetyl CoA through generation of ketone bodies. HMGCS2 is generally expressed in liver where it converts acetyl-CoA to ketone bodies. Although the expression of HMGCS2 was detected in extra-hepatic organs, its role is undefined. We recently showed that HMGCS2 was most upregulated gene in type 1 diabetic heart of mice model which is also an indirect reflection of exaggerated HMGCS2 activity. Our long term goals are to investigate new mechanism for entrée into pathways that will modulate HMGCS2-induced cardiac dysfunction during diabetes insults which will provide a strong empirical basis for pursuing therapeutic target gene(s) in the treatment or prophylaxis of heart failure in diabetic patients.