Charles E. Sparks, M.D.

Charles E. Sparks, M.D.

Contact Information

University of Rochester Medical Center
School of Medicine and Dentistry
601 Elmwood Ave, Box 608
Rochester, NY 14642

Office: (585) 275-8236
Fax: (585) 756-5337

Research Bio

Apo B exists as B48 and B100 produced through a novel posttranscriptive mechanism of apo B mRNA editing producing protein products of differing size with differing metabolisms. The goal of our research is to understand apo B triglyceride-rich lipoprotein (TRL) assembly contrasting B100 and B48 synthetic pathways. McArdle RH-7777 cells (McA) have provided many useful insights into inherent differences in B100 and B48 in TRL biogenesis. Recent studies indicate that B100-TRL assembly occurs by lipidation of conformationally "acceptable" B100. B48 undergoes initial lipidation similar to B100 followed by neutral lipidation of the precursor high density lipoprotein particle (B48-HDL) to form B48-TRL. More than 70% of the triglyceride (TG) fatty acids (FA) arise from cytosolic, stored TG through a process involving lipolysis/reesterification. Lipolyzed FAs, possibly through acylation reactions with PL intermediates, traverse the ER membrane by unknown means prior to fusion with B48-HDL. Unlike B100, that is synthesized and rapidly secreted by rat hepatocytes (RH), there is a kinetically distinct pool of B48 that has a long cellular retention time. We hypothesize that this pool may provide a ready supply of B48-HDL as a precursor for the rapid assembly of TRL via a later assembly step. In cells that make predominantly B48, such as intestine, the cellular pool of B48 allows TRL secretion to occur without a requirement for de novo apo B synthesis. We recently identified a novel protein factor, an apo B secretion enhancer (BSE), whose expression correlates with apo B mRNA abundance in McA cells transfected with BSE. Apo B mRNA abundance, however, does not correspond with a proportional increase in apo B secretion. Studies explore the role of BSE in the observed changes in apo B mRNA stability/transcription. Apo B degradation studies address the non-proportional secretory rate. A phospholipid (PL)-dependent pathway for the stimulation of apo B secretion by BSE is suggested as BSE is homologous with betaine homocysteine methyltransferase (BHMT), a methylation enzyme. An hypothesis explored is that, apart from its ability to stabilize apo B mRNA, an ER form of BSE may provide newly synthesized phosphatidylcholine (PC) via phosphatidylethanolamine (PE) methylation of phosphatidylserine (PS) and increased supply of PL may be a mechanism for the enhancing secretion of apo B.



Importance of the research is related to the role of apo B in lipid transport and as a factor associated with risk of arterial disease. Additional research focuses on the role of apo B as a risk factor in developing heart attacks, strokes, and in recurrent heart attacks in human populations.

Awards & Honors (Local)

Secretarial Appointee. Department of Veterans Affairs Medical Research Service Merit Review Subcommittee for Endocrinology (Chair: Endocrinology-A Review Board, Fall 2003, Spring & Fall 2004) 2002 - 2005
Co-Chair. Thrombogenic Factors and Recurrent Coronary Events Symposium, Perugia, Italy 1998
Co-Chair. National Symposium Meeting, American Diabetes Association, Lipoproteins, Diabetes and Atherosclerosis. 1988
Invited Speaker. Gordon Research Conference on Atherosclerosis: "Is intestinal apo B a determinant for lipoprotein recognition?" 1981
Conferee. Lipid Metabolism and Atherosclerosis, 1978, '79, '80, '81, '84, '86, '88, '90, '92, '96, '00, '04 Gordon Research Conference, Kimball Union Academy, Meriden, NH 1978 - 2004
Individual Research Service Award Grantee, National Institutes of Health 1975 - 1977
Chief Resident in Pathology, University of Pennsylvania 1974 - 1975

Patents

Serum Glocose and Triglyceride Determine High-Risk Subgroups in Non-diabetic Postinfarction Patients

United States Serial NO.: 11/809,832
Filed Date: May 31, 2007
Title: Indentifying Risk of a Medical Event
Invented by: James Corsetti, Charles Sparks, Daniel Ryan, Arthur Moss

Recent Journal Articles

Showing the 5 most recent journal articles. 96 available »

2014 Jun
Sparks CE, Corsetti JP, Sparks JD. "High-density lipoproteins: taking the good with the bad." Current opinion in lipidology. 2014 Jun; 25(3):230-2.
2014 May 22
Corsetti JP, Gansevoort RT, Bakker SJ, Sparks CE, Vart P, Dullaart RP. "Apolipoprotein B Attenuates Albuminuria-Associated Cardiovascular Disease in Prevention of Renal and Vascular Endstage Disease (PREVEND) Participants." Journal of the American Society of Nephrology : JASN. 2014 May 22; Epub 2014 May 22.
2013 Oct
Sparks CE, Sparks JD. "Hepatic postprandial transition and very low-density lipoprotein biogenesis." Current opinion in lipidology. 2013 Oct; 24(5):450-2.
2013
Corsetti JP, Salzman P, Ryan D, Moss AJ, Zareba W, Sparks CE. "Plasminogen activator inhibitor-2 polymorphism associates with recurrent coronary event risk in patients with high HDL and C-reactive protein levels." PloS one. 2013 8(7):e68920. Epub 2013 Jul 09.
2012 Sep
Sparks JD, Sparks CE, Adeli K. "Selective hepatic insulin resistance, VLDL overproduction, and hypertriglyceridemia." Arteriosclerosis, thrombosis, and vascular biology. 2012 Sep; 32(9):2104-12. Epub 2012 Jul 12.

Current Appointments

Professor Emeritus - Department of Pathology and Laboratory Medicine (SMD) - Primary

Specialties

Clinical Pathology/Laboratory Medicine - American Board of Pathology

Education

MD | Medicine | Jefferson Medical College1968
BS | Biochemistry | Mass Inst Technology1963

Post-Doctoral Training & Residency

Fellow, Biochemistry Medical College of Pennsylvania 1977
Fellow, Cardiopulmonary Medicine University of Pennsylvania 1976
Resident Hospital of the University of Pennsylvania (Clinical Pathology) 1975
Intern New York Hospital, Cornell (Medicine) Naval Hospital, St. Albans (Rotating) 1969