Peeyush K. Lala

Genetics & Development Dr. Peeyush K Lala
Associate Scientist
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Affiliations

Associate Scientist, Division of Genetics & Development, Children’s Health Research Institute
Professor, Departments of Anatomy and Cell Biology and Oncology, Schulich School of Medicine & Dentistry, Western University

How my research helps children

My research dealing with the human placenta is crucial to the health of unborn and new born children and their health during post-natal life. The human placenta is a highly invasive “tumor-like” structure that must invade the pregnant uterus and its arteries to tap on the maternal blood supply and nourish the fetus. Unlike tumors, this invasion is exquisitely controlled by certain locally-derived molecules, so that the mother remains unharmed. Poor placental invasion results in reduced flow of maternal blood to the placenta. This, in turn, can result in spontaneous abortion or fetal growth restriction and a serious pregnancy-associated maternal disease called preeclampsia. Growth–restricted newborns have a higher risk of developing diabetes and heart disease in later life. Conversely, excessive and unrestricted placental invasion is a sign of placental tumors.

Our research has uncovered and identified key molecules made locally by the placenta and the pregnant uterus that coordinate placental invasion in a balanced and healthy manner so that fetal or maternal health remains uncompromised. However, this can go wrong in a significant proportion of pregnancies. Can we catch them before it is too late? We are exploring whether the production and activity of the invasion–controlling molecules can be monitored in the pregnant mother as a predictor of healthy or poor placental invasion, so that we can prevent poor fetal growth or development of preeclampsia in the mother.

Our research on the placenta has also advanced cancer research. We have discovered that placental tumor cells resist the action of the invasion-controlling molecules that apply to normal placental cells. We have identified certain molecular and genetic changes that are responsible for this defiance and the conversion of normal placental cell populations into precancerous and then cancerous cells. This information applies to many other cancers.

Research

Current Research

We have recently discovered that a molecule called decorin made by the pregnant uterus plays a key role in restraining placental invasion of the uterus. We are currently investigating the mechanisms of action of this molecule and whether their derangements in early pregnancy can predict preeclampsia in the mother and or restricted growth of the fetus.

Research Team

Two post-doctoral fellows-- Drs Gannareddy Girish and Dr Gausal Khan, and three graduate students—Catalin Nicola (PhD), Daniel Iacob (Msc) and Neena Lala (Msc) have contributed significantly to our recent or ongoing research, resulting in major publications. The picture of invasive placental cells in an article published by Catalin Nicola was highlighted on the cover page of the Biology of Reproduction vol 78, number 6, June 2008.

Future Research Plans

We are collaborating with Drs Victor Han and Andy Babwah at the CHRI on the role of decorin dysfunction in preeclampsia and Dr Lynne Postovit on the identity and regulation of stem cells in the placenta that give rise to the invasive placental cells.

Awards & Grants

Awards & Grants (past 5 years)

Funding in support of Biology of the fetomaternal interface – Awarded by Canadian Institute of Health Research (CIHR)

Funding in support of COX-2 mediated induction of stem cells in human breast cancer and identification of therapeutic targets – Awarded by Ontario Institute of Cancer Research (OICR)

Awarded Breast Cancer Society of Canada Fellowship

Awarded Canadian Breast Cancer Foundation (CBCF) Fellowship

Fellowship for Breast Cancer Research – Awarded by Susan Komen Foundation, USA

Funding in support of Biology of the fetomaternal interface – Awarded by Canadian Institute of Health Research (CIHR)

Funding in support of Regulation of lymphangiogenesis and lymphatic metastasis in a murine breast cancer model – Awarded by Canadian Breast Cancer Foundation (CBCF)

Funding in support of COX-2/Her2 neu axis in VEGF-C upregulation and Breast Cancer Therapy – Awarded by Ontario Institute for Cancer Research (OICR)

Funding in support of Role of VEGF-C in breast cancer progression and metastasis – Awarded by Canadian Breast Cancer Foundation (CBCF)

Recent Publications

Publications

A practical and sensitive method of quantitating lymphangiogenesis in vivo
Majumder M, Xin X, Lala PK
Lab Invest. 2013 May

Mechanisms in Decorin regulation of Vascular Endothelial Growth Factor-induced Human Trophoblast Migration and Acquisition of Endothelial Phenotype
Lala N, Girish G V, Cloutier-Bosworth A, Lala PK
Biology of Reproduction. 2012; 87(3):59, 1-14; before print June 13, 2012, doi:10.1095/biolreprod.111.097881

Targeting COX-2 and EP4 to Control Tumor Growth, Angiogenesis, Lymphangiogenesis and Metastasis to the Lungs and Lymph Nodes in a Mouse Breast Cancer Model
Xin X, Majumder M, Girish G, Mohindra V, Maruyama T and Lala PK
Lab Investigation. 2012; 92:1115–1128; doi:10.1038/labinvest. 2012.90; published online 28 May 2012

Co-expression of α9β1 integrin and VEGF-D confers lymphatic metastatic phenotype to a human breast cancer cell line MDA-MB-468LN
Majumder M, Tutunea-Fatan E, Xin X, Rodriguez-Torre M, Torres-Garcia J , Wiebe R, Timoshenko AV, Bhattacharjee RN, Chambers AF, Lala, PK
PLoS One.  2012; 7(4):e35094. doi:10.1371/journal.pone.0035094

Decorin is a Novel VEGFR-2-Binding Antagonist for the Human Extravillous Trophoblast
Khan GA, Girish GV, Lala N, DiGuglielmo GM, Lala PK
Mol Endocrinology. 2011 June 9 [Epub ahead of print]

Decorin-mediated inhibition of proliferation and migration of the human trophoblast via different tyrosine kinase receptors
Iacob D, Cai J, Tsonis M, Babwah A, Chakraborty C, Bhattacharjee RN, Lala PK
Endocrinology. 2008; 149(12):6187-97

Elevated expression of serine protease HtrA1 inn preeclampsia and its role in trophoblast migration and invasion
Ajayai F, Congosa N, Gaffey T, Asman YW, Watson W, Baldi A, Lala PK, Shridhar V, Brost B, Chien J
Amer J Obstet Gynecol. 2008 November; 199, issue 5, 557.e1-557.e10

Prostaglandin(PG)E2-mediated migration of human trophoblast requires Rac1 and Cdc42 GTPases
Nicola C, Lala PK, Chakraborty C
Biol Reprod. 2008; 78:976-982

Roles of Rho guanosine triphosphatase A, Rho kinases and extracellular signal regulated kinases (1/2) in Prostaglandin E2-mediated migration of first trimester human extravillous trophoblast
Nicola C, Chirpac A, Lala PK, Chakraborty C
Endocrinology. 2008 Mar; 149(3):1243-51

Migration-promoting role of VEGF-C and VEGF-C binding receptors. in human breast cancer cells
Timoshenko AV, Rastogi S, Lala PK
Brit J Cancer. 2007; 97(10):1090-1098

Additional publications

Contact

Contact

Phone: (519) 661-3015
Fax: 519-661-3936
Email: pklala [at] uwo [dot] ca
Website: http://www.uwo.ca/anatomy/department/lalap/plala.html

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