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Iron and Pregnancy: Regulatory Mechanisms and Adverse Outcomes

Award Number: K01DK127004
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 02/01/2021
PERIOD OF PERFORMANCE END DATE: 01/31/2026

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Iron and Pregnancy: Regulatory Mechanisms and Adverse Outcomes - PROJECT SUMMARY/ABSTRACT I am a post-doctoral scientist interested in the regulation of metabolic processes important to human health and the pathophysiology of human diseases. My long-term goal is to become an expert and academic leader in the field of iron homeostasis, answering questions and developing applications relevant to human health and disease. I aim to expand the field of iron homeostasis to the previously neglected area of iron regulation during pregnancy and the contribution of iron disorders to adverse pregnancy outcomes, and apply these discoveries beyond pregnancy, to other common iron disorders. I will be supported by my primary mentor, Dr. Elizabeta Nemeth, a leader in the field of anemia and iron metabolism, along with co-mentors who will contribute their multidisciplinary expertise to train me in theoretical and methodological aspects of placental and fetal health and disease. Through UCLA’s Clinical and Translational Science Institute (CTSI), I will choose from numerous career development seminars that address such topics as grant writing, manuscript preparation, and ethical research. I will also take graduate courses to obtain further training in immunology, developmental biology, bioinformatics and biostatistics. I feel fortunate to have the full support of my institution, as well as the many advantages of carrying out my research project at the University of California Los Angeles, a renowned research center. This proposal outlines a 5-year research and career development plan that will prepare me to become an independent scientist engaged in cutting-edge scientific research. This project aims to identify the pregnancy- related hepcidin suppressor and elucidate the mechanisms mediating adverse interaction between iron deficiency and inflammation during and outside of pregnancy. Although iron availability during pregnancy is highly regulated, the regulatory mechanisms are not well understood. Using an in vitro bioassay to detect hepcidin suppressive activity, I identified the trophoblast as the source of a potent and robust hepcidin suppressor. Specific Aim 1a seeks to isolate and identify the trophoblast-derived hepcidin suppressor using an orthogonal multi-step protein purification approach. Specific Aim 1b seeks to examine the mechanisms involved in trophoblast-mediated hepcidin suppression, including the role of ALK2 ubiquitination. Iron disorders of pregnancy and their interaction with inflammation commonly contribute to adverse maternal and fetal outcomes. My preliminary data suggest the role of the TNFα-TNFR1 pathway in this process. For specific Aim 2a, I will define the mechanism(s) of TNF-receptor regulation by iron deficiency and in Specific Aim 2b, determine the contribution of TNF-receptor and inflammatory cytokines to adverse interaction between inflammation and iron deficiency observed in our mouse models. This project has important and broad translation potential, and seeks to answer high-impact mechanistic questions about the regulation of iron during pregnancy and iron pathologies outside of pregnancy. While developing my full potential as a scientist, I aim to expand our knowledge of iron disorders in pregnancy and in other disease states where iron dysregulation contributes to their pathogenesis.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $151,805 )
2025	2025	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	2/19/2025	NON-COMPETING CONTINUATION	$151,805
														Subtotal = $151,805

Issue Date FY: 2024 ( Subtotal = $151,805 )
2024	2024	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	1/22/2024	NON-COMPETING CONTINUATION	$151,805
														Subtotal = $151,805

Issue Date FY: 2023 ( Subtotal = $151,805 )
2023	2023	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	2/17/2023	NON-COMPETING CONTINUATION	$151,805
														Subtotal = $151,805

Issue Date FY: 2022 ( Subtotal = $151,805 )
2022	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	1/28/2022	NON-COMPETING CONTINUATION	$151,805
														Subtotal = $151,805

Issue Date FY: 2021 ( Subtotal = $153,305 )
2021	2021	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	1/8/2021	NEW	$153,305
														Subtotal = $153,305

Grand Total All Awards = $760,525

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Iron and Pregnancy: Regulatory Mechanisms and Adverse Outcomes

Award Number: K01DK127004

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 02/01/2021

PERIOD OF PERFORMANCE END DATE: 01/31/2026

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