Cornell University, Ithaca, NY , Ph.D., 1978 

Research Summary
Research in my lab is aimed at understanding the  processes of lipid absorption and metabolism. These studies are especially  relevant because of the rapid increase in obesity in developed countries and  the consequent rise in Type II diabetes. In addition, hyperlipidemia is a  major risk factor for cardiovascular diseases which remain a major couse of morbidity and mortality in "Western" cultures.

One project is focused on elucidating the intracellular  steps and cellular machinery that are involved in lipid absorption and  chylomicron production by the intestinal epithelium. The second project is  focused on the selective uptake of cholesterol esters from HDL by hepatocytes  and the subsequent processing of that cholesterol for bile acid synthesis, lipoprotein production or secretion as biliary cholesterol.

Both projects utilize knockout mice in which the gene  for carboxyl ester lipase (CEL, cholesterol esterase, bile salt stimulated  lipase) has been ablated. During active lipid absorption, these mice produce  intestinal lipoproteins that are dramaticlly different in size and protein composition, suggesting that enzyme plays an important role in chylomicron synthesis and/or secretion - most likely by affecting Golgi function. Absence  of a functional CEL gene also appears to alter the processing of HDL-cholesterol  by hepatocytes, resulting in changes in bile acid production and biliary  cholesterol secretion.

1. Howles, P., C. Carter, and D. Hui (1996). Dietary free and esterified cholesterol absorption in cholesterol esterase (bile  salt-stimulated lipase) gene-targeted mice. Journal of Biological  Chemistry 271:7196-7202.

2. Carter, C., P. Howles, and D. Hui (1997). Genetic variation in cholesterol absorption efficiency among inbred strains of  mice. Journal of Nutrition 127:1344-1348.

3. Howles, P., G. Stemmerman, C. Fenoglio-Preiser, and  D. Y. Hui (1999). Carboxyl ester lipase activity in milk prevents  fat-derived intestinal injury in neonatal mice. American Journal of  Physiology 277:G653-G661.

4. Abonia, J., P. Howles, K. Abel, T. Black, C. Jones and K. Gross (2001). Evaluating a model of NRE-mediated tissue-specific  expression of the murine renin genes. Hypertension 37:105-109.

5. Cai, S., J. Kirby, P. Howles and D. Hui (2001). Differentiation-dependent expression and localization of the class B type  I scavenger receptor in intestine. Journal of Lipid Research 42:902-909.

6. Shen, H., P. Howles and P. Tso (2001). From interaction of lipidic vehicles with intestinal epithelial cell membranes  to the formation and secretion of chylomicrons. Advances in drug delivery  50(suppl. 1):S103-125 (Review).

7. Kirby, J., S. Cheng, P. Tso, P. Howles and D.Hui (2002). Bile salt-stimulated carboxyl ester lipase influences lipoprotein  assembly and secretion in intestine. Journal of Biological Chemistry  277:4104-4109.

8. Howles, P, B. Wagner, A. Gupta, and C. Carter. Pancreatic carboxyl ester lipase can increase digestion and absorption of  retinyl palmitate in mice. (submitted to European Journal of Biochemistry)

9. Woollett, L., D. Strickland, D. Hui, and P. Howles. Megalin expression in the small intestine of neonatal mice: possible role  of development and RAP. (submitted to Journal of Histochmistry and Cell  Biology).

10. Wagner, B., L. Davis and P. Howles. Milk-derived carboxyl ester lipase is necessary for fat digestion and absorption in  neonatal mice. (in preparation for Journal of Lipid Research)

11. Howles, P. and B. Lewandowski. Reduced hepatic vitamin A stores in neonatal mice lacking carboxyl ester lipase. (in  preparation for Journal of Pediatric Gastroenterology & Nutrition)

BOOK CHAPTERS

1. Howles, P. and D. Hui (2001). Cholesterol Esterase. In Intestinal Lipid Metabolism (C. Mansbach, A Kuksis and P. Tso,  editors), p.119-134, Kluwer Academic/Plenum Publishers, New York.

2. Nikiforov, Y and P. Howles (2001). Polymerase Chain  Reaction. In Morphology Methods: Cell and Molecular Biology Techniques (R.  Lloyd, editor), p.181-207. Humana Press, Totowa, New Jersey.