Research Summary

Our laboratory primarily investigates the use of angiogenic biomarkers for the prediction of preclampsia related adverse maternal and fetal outcomes. We believe that these biomarkers can be used for the risk stratification of patients with hypertensive disorders of pregnancy, especially when measured in the third trimester. This may help prevent unnecessary iatrogenic preterm deliveries and allow the allocation of scarce resources to patients with the most severe disease in low resource settings.  In one of our early studies we were able to demonstrate that women who have preeclampsia related thrombocytopenia have a different angiogenic profile than women with gestational and idiopathic thrombocytopenia unrelated to preeclampsia (Young et al, J Matern Fetal Neonatal Med. 2010). We were also able to link a systemic angiogenic imbalance, accentuated by preeclampsia, with peripartum cardiomyopathy (PPCM).(Patten et al, Nature. 2012). We later conducted a clinical study which investigated whether angiogenic factors could enable clinicians to differentiate preeclampsia from other hypertensive disorders in women presenting to triage with symptoms of preeclampsia. The results from this study, “Angiogenic Factors and the Risk of Adverse Outcomes in Women with Suspected Preeclampsia”, were published in Circulation (2012). This data was also analyzed in relation to twin pregnancies and the presence of soluble endoglin in the plasma of these patients. The measurable differences that were found in women with and without adverse outcomes led us to develop a risk calculator for the prediction of adverse outcomes (Palomaki et al, Prenat Diagn, 2015 ). More recently we found that the antepartum angiogenic profile positively correlated with blood pressures in the postpartum period and was independently associated with postpartum hypertension in multivariable analysis. The observation that abnormalities in angiogenic factors are associated with postpartum hypertension suggests that women with pathophysiologic features of preeclampsia are especially at risk, since these biomarkers have been shown to reliably distinguish preeclampsia from other forms of hypertensive disorders in pregnancy (Goel et al, Circulation, 2015).
Our research also extended to Hôpital Albert Schweitzer (HAS) in Haiti, which has the world’s highest rates of preeclampsia-related maternal and fetal/neonatal mortality. Our early studies had revealed that the current diagnostic criteria for preeclampsia very poorly predicted adverse outcomes in Haiti (Raghuraman N, Pregnancy Hypertens. 2014) and that angiogenic factors are closely related to adverse outcomes associated with preeclampsia regardless of gestational age (March MI, PLoS One. 2015).  We are testing the idea that novel angiogenic biomarkers will prove to be superior in predicting adverse outcomes, leading to dramatic reductions in maternal and fetal mortality related to preeclampsia. Since preeclampsia is a major cause of maternal and neonatal morbidity and mortality globally, our long-term goal is to contribute to the reduction, if not the elimination, of the terrible outcomes associated with this disease.
In 2014, the Rana laboratory was established at the University of Chicago Medicine, where Dr. Rana had taken the position of Chief of the Section of Maternal-Fetal Medicine in the Department of Obstetrics & Gynecology.

Current research:

  1. Use of angiogenic biomarkers for prediction of adverse outcomes among women with suspected preeclampsia

  2. Echocardiographic changes in women with preeclampsia

  3. Identifying risk factors for maternal and fetal death related to preeclampsia in Haiti

  4. Use of small molecules that inhibit sFlt1 as a potential treatment of preeclampsia

  5. Study epidemiology and mechanisms of postpartum hypertension

Rana S, Powe CE, Salahuddin S, Verlohren S, Perschel FH, Levine RJ, Lim KH, Wenger JB, Thadhani R, Karumanchi SA. Angiogenic Factors and the Risk of Adverse Outcomes in Women with Suspected Preeclampsia. Circulation. 2012; 125(7): 911-9.

Patten IS#, Rana S#, Shahul S, Rowe GC, Jang C, Liu L, Hacker MR, Rhee JS, Mitchell J, Mahmood F, Hess P, Farrell C, Koulisis N, Khankin EV, Burke SD, Tudorache I, Bauersachs J, Monte F , Hilfiker-Kleiner D, Karumanchi SA , Arany Z. Cardiac Angiogenic Imbalance Leads to Peri-partum Cardiomyopathy. Nature. 2012; 485: 333–338.  #equal contribution.

March MI, Geahchan C, Wenger J, Raghuraman N, Berg A, Haddow H, Mckeon BA, Narcisse R,  David JL,  Scott J, Thadhani R, Karumanchi SA, Rana S. Circulating Angiogenic Factors and the Risk of Adverse Outcomes among Haitian Women with Preeclampsia. PLoS One. 2015 May 12; 10(5): e0126815.

Rana S, Rajakumar A, Geahchan C, Salahuddin S, Cerdeira AS, Burke S, George E, Granger J, Karumanchi SA. Ouabain Downregulates sFlt1 Production by Inhibiting HSP27-Dependent HIF-1a Protein Expression. FASEB J. 2014; 28(10): 4324-34.

 

Goel A, Maski MR, Bajracharya S, Wenger JB, Zhang D, Salahuddin S, Shahul S, Thadhani R, Seely EW, Karumanchi SA, Rana S. Epidemiology and Mechanisms of De Novo Hypertension in the Postpartum Period. 2015. Circulation. 2015 Nov 3;132 (18):1726-33.

 

 


 
Sarosh Rana, MD, MPH

Associate Professor
Chief, Section of Maternal-Fetal Medicine
The University of Chicago
See Dr. Rana's Clinical Bio

Contact Information

E-mail: srana@bsd.uchicago.edu
Mailing address:
Sarosh Ranal, MD, MPH
Department of OBGYN, MC 2050
Chicago, Ill. 60637, USA

Administrative Assistant:
Amelia Donovan
Phone: 773-834-4012

Dr. Rana is currently the director of an OBGYN Transitional Research Fellowship. Click here for more information