Research Interests

Determining the molecular mechanisms of fetal programming.

Our laboratory is interested in determining the basis of fetal programming. What is fetal programming? About two decades ago, researchers in England discovered an unusual pattern in who got heart disease. It was assumed that affluent individuals who had a higher standard of living would have a higher rate of heart disease than individuals that grew up in poorer areas. They would have a richer caloric intake and would develop blocked arteries and eventual heart disease. What researchers found was the opposite. Heart disease was higher in areas where people had grown up in poorer areas. The researchers eventually came to the conclusion that the fetal environment such as the nutrient intake by a mother could have a permanent or ‘programmed’ effect on the offspring.  Since that early observation, researchers have found that not only heart disease but also diabetes, obesity, appetite level, hypertension, and possibly cancer can be impacted by fetal programming. This may explain why the propensity of some people to be obese while others can eat as much as they want without a big effect. How this occurs on a molecular level is a research focus of my laboratory.

We have been examining fetal programming by giving rat mothers a restricted diet during gestation. Once the pups are born, we measure fat accumulation, kidney function, appetite, behavior, glucose tolerance, and other factors. We have found that ‘maternal food restricted’ pups are changed in genes that control fat accumulation (increase in PPAR gamma, a mediator of fat biosynthesis genes), in kidney function (decreased expression of the GDNF-cRET-WNT11 pathway), and in appetite (changes in NPY).

My current research is focused on understanding the molecular changes in kidney that would explain the increased hypertension seen in maternal food restricted adults. We use kidney explants, which are kidneys that are removed from fetal rats and cultured for several days in media. The kidneys continue to grow and we can examine the effect of blocking or increasing key proteins that control the developing kidney morphology.

In addition, to this research, I am collaborating with researchers in my previous laboratory, Drs. Monica Ferrini, Nestor-Gonzalez-Cadavid, and Robert Gelfand  and also with fellow Drew scientist Jorge Artaza, in the use of myostatin gene vectors to control skeletal and smooth muscle function and differentiation. We are using gene therapy which is a process where a DNA molecule, a gene, is given to an organ or tissue and it replaces, increases or decreases that specific gene, thereby correcting the disease. For example, sickle cell anemia disease is caused by a single mutation in the hemoglobin beta gene which leads to defective red blood cells. Within the last few years, researchers have been able to introduce ‘good’ hemoglobin beta genes into sickle cell diseased mice and correct the disease. We are currently designing new vector to tackle a variety of projects including fetal programming.