Sood Laboratory

Location

Translational & Biomedical Resource Center
4th Floor

General Interests

Placental Development, Blood Coagulation, Uterine Hemostasis, Obstetric Hemorrhage, Perinatal health/Prematurity, Preeclampsia

View Rashmi Sood Bio

Research Areas

Regulation of placental and uterine hemostasis

Humans form a hemochorial placenta. In this type of placentation, the walls of maternal arteries leading to the placenta are breached and maternal blood flows through extravascular spaces lined by zygote-derived cells. There remain fundamental gaps in knowledge on how blood coagulation is regulated and hemorrhage is prevented during hemochorial placentation and in parturition. Hallmarks of pathological thrombosis in uteroplacental circulation are poorly defined. The unusual blood flow in hemochorial placentation is thought to further increase the risk of thrombosis in women with preexisting clotting disorders, and contribute to recurrent pregnancy loss, fetal growth restriction, stillbirth, and other placenta-mediated pregnancy complications. Conversely, inflammation can trigger excessive coagulation in the placenta causing pregnancy complications. Obstetric hemorrhage remains a leading cause of maternal death worldwide. Given the high incidence of these pregnancy complications and their severe consequences on maternal and fetal health, it is necessary to identify (1) key factors that regulate placental and uterine hemostasis, and (2) features that mark pathological thrombosis. To address this gap in knowledge, we generate and utilize murine models of maternal and fetal thrombophilia to examine the role of thrombotic processes in uteroplacental disease and its consequences on maternal and fetal health.

Learn More

Endothelial Protein C Receptor plays an essential role in the maintenance of pregnancy
Absence of platelet thrombin receptor PAR4 prevents thrombotic and stroke-like phenotypes of thrombomodulin deficient mice
Genetic Absence of Integrin αIIb improves survival of Tissue factor Pathway inhibitor Null Mice but Results in Hydrocephalus Formation
Animal Models Demonstrate a Critical Role of Factor VIII in Par4- and Platelet-Mediated Pathology

Human pregnancy and gestational syndromes

Prediction and prevention of gestational syndromes such as preeclampsia and spontaneous preterm delivery are a crucial challenge facing modern obstetrics. The placenta plays a key role in these complications. In the United States, about 1 in 10 babies are born before 37 weeks of gestation. It is a leading cause of neonatal death and the second leading cause of death below 5 years of age. Preterm babies that survive the neonatal period are predisposed to long-term health complications. Preeclampsia is another complex gestational syndrome that roughly affects 5 to 7% of all pregnancies. It is most typically characterized by maternal hypertension and proteinuria. Preeclampsia is frequently associated with fetal growth restriction and often requires premature delivery, putting neonates at risk of immediate and long-term adverse health consequences. It can progress into its potentially fatal form eclampsia and endanger the lives of the mother and fetus. There is a paucity of tools to monitor healthy progression of pregnancies and predict the risk of these major gestational syndromes. Our laboratory utilizes a sensitive bioassay to identify changes in maternal plasma associated with normal progression of pregnancy and abnormalities that are predictive of preterm birth and preeclampsia. In recent work conducted through funding from Advancing a Healthier Wisconsin Endowment, we find that features identified by this assay allow correct classification of preterm birth cases and normal term controls with 90% accuracy 8 weeks prior to preterm delivery. Our goal is to identify features that can be developed into useful biomarkers for prediction and early diagnosis.

Current Members

Michelle Castillo, PhD

Postdoctoral Fellow

mcastillo@mcw.edu

Katelyn Storage

Lab Technician

kstorage@mcw.edu

Summer 2018

Pictured left to right: Katelyn Storage, Kathryn Wagstaff, Emily Ott, Michelle Castillo, Dosia McKinney, Abril Solis Sigala, Rashmi Sood, Qiuhui Yang

Summer 2016

Pictured left to right, back row: Qiuhui Yang, Michelle Bordas, Alicia Ivory, Rashmi Sood, Michelle Castillo; front row: Kristen Chen, Katelyn Storage, Alli Biskowitz

The endothelial protein C receptor plays an essential role in the maintenance of pregnancy.

(Castillo MM, Yang Q, Sigala AS, McKinney DT, Zhan M, Chen KL, Jarzembowski JA, Sood R.) Sci Adv. 2020 Nov;6(45) PMID: 33158859 PMCID: PMC7673707 SCOPUS ID: 2-s2.0-85095802928 11/08/2020
Maintaining extraembryonic expression allows generation of mice with severe tissue factor pathway inhibitor deficiency.

(Castillo MM, Yang Q, Zhan M, Pan AY, Lawlor MW, Mast AE, Sood R.) Blood Adv. 2019 Feb 12;3(3):489-498 PMID: 30755437 PMCID: PMC6373739 SCOPUS ID: 2-s2.0-85061474836 02/14/2019
Humanized GPIbα-von Willebrand factor interaction in the mouse.

(Kanaji S, Orje JN, Kanaji T, Kamikubo Y, Morodomi Y, Chen Y, Zarpellon A, Eberhardt J, Forli S, Fahs SA, Sood R, Haberichter SL, Montgomery RR, Ruggeri ZM.) Blood Adv. 2018 Oct 09;2(19):2522-2532 PMID: 30287479 PMCID: PMC6177644 SCOPUS ID: 2-s2.0-85069786057 10/06/2018
Variable phenotypic penetrance of thrombosis in adult mice after tissue-selective and temporally controlled Thbd gene inactivation.

(van Mens TE, Liang HH, Basu S, Hernandez I, Zogg M, May J, Zhan M, Yang Q, Foeckler J, Kalloway S, Sood R, Karlson CS, Weiler H.) Blood Adv. 2017 Jun 27;1(15):1148-1158 PMID: 28920104 PMCID: PMC5600150 09/19/2017
The Endothelial Protein C Receptor plays an essential role in the maintenance of Pregnancy

(Castillo MM, Yang Q, Sigala AS, McKinney DT, Zhan M, Chen KL, Jarzembowski JA, Sood R.) BioRxiv. https://doi.org/10.1101/2020.02.05.935940 02/05/2020
Deficiency of Protease Activated Receptor 3 in the Mother Prevents Placenta-Mediated Death of Endothelial Protein C Receptor Null Mice, but Uncovers an Obligate Requirement of EPCR in the Embryo and Neonate.

(Castillo MM, Yang Q, Sood R.) Blood. 134 (Supplement_1): 2382; https://doi.org/10.1182/blood-2019-131453 11/13/2019
Genetic Absence of Integrin alpha2b Improves Survival of Tissue Factor Pathway Inhibitor Null Mice but Results in Hydrocephalus Formation

(Castillo M, Ott E, Wujek R, Qiuli L, Schmainda K, Cohen S, Sood R.) Blood. 134 (Supplement_1): 3626; https://doi.org/10.1182/blood-2019-131811 11/13/2019
Animal Models Demonstrate a Critical Role of Factor VIII in Par4-and Platelet-Mediated Pathology

(Castillo M, Yang Q, McKinney D, Shi Q, Sood R.) Blood. 134 (Supplement_1): 1057; https://doi.org/10.1182/blood-2019-123290 11/13/2019
Absence of platelet thrombin receptor PAR4 prevents thrombotic and stroke-like phenotypes of thrombomodulin deficient mice

(Storage M, Yang Q, Zhan M, Sood R.) Res Pract Thromb Haemost. 1 (S1): 87; OC 02.5; https://doi.org/10.1002/rth2.12012 06/23/2017
Maintaining extraembryonic expression allows generation of adult mice with Tissue Factor Pathway Inhibitor gene disruption

(Storage M, Yang Q, Zhan M, Sood R.) Res Pract Thromb Haemost. 1 (S1): 86; OC 02.1; https://doi.org/10.1002/rth2.12012 06/23/2017
Vasculogenesis and Angiogenesis

(Chun CZ, Sood R, Ramchandran R.) In: North P., Sander T. (eds) Vascular Tumors and Developmental Malformations.. Molecular and Translational Medicine. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-3240-5_3 01/01/2016
Genetic Absence of Thrombin Receptor Par4 Overcomes the Obligate Requirement of EPCR in Mouse Placenta

(Storage MM, An J, Liang H, Yang Q, Zogg M, Zhan M, Weiler H, Sood R.) Blood. 126 (23): 425; https://doi.org/10.1182/blood.V126.23.425.425 12/03/2015