Holly Ingraham, PhD

Professor
Cellular Molecular Pharmacology
+1 415 476-3401

The Ingraham Lab investigates mammalian sex-differences and how hormone signaling in the brain and in the gut-brain axis affects sex-dependent physiological endpoints in females, especially during aging.

Publications: 

An evolutionary trade-off between host immunity and metabolism drives fatty liver in male mice.

Science (New York, N.Y.)

Nikkanen J, Leong YA, Krause WC, Dermadi D, Maschek JA, Van Ry T, Cox JE, Weiss EJ, Gokcumen O, Chawla A, Ingraham HA

Running the Female Power Grid Across Lifespan Through Brain Estrogen Signaling.

Annual review of physiology

Ingraham HA, Herber CB, Krause WC

Oestrogen engages brain MC4R signalling to drive physical activity in female mice.

Nature

Krause WC, Rodriguez R, Gegenhuber B, Matharu N, Rodriguez AN, Padilla-Roger AM, Toma K, Herber CB, Correa SM, Duan X, Ahituv N, Tollkuhn J, Ingraham HA

Chronic Stimulation of Arcuate Kiss1 Neurons Decreases Bone Mass in Female Mice.

Journal of the Endocrine Society

Ruben Rodriguez, Candice B Herber, William C Krause, Holly A Ingraham

SPARC - Mapping Gut-Spinal Cord Connections in Visceral Pain.

The FASEB Journal

Ryan David Morrie, James Bayrer, Stuart Brierley, Holly Ingraham, David Julius

Should We Make More Bone or Not, As Told by Kisspeptin Neurons in the Arcuate Nucleus.

Seminars in reproductive medicine

Herber CB, Ingraham HA

Estrogen signaling in arcuate Kiss1 neurons suppresses a sex-dependent female circuit promoting dense strong bones.

Herber CB, Krause WC, Wang L, Bayrer JR, Li A, Schmitz M, Fields A, Ford B, Zhang Z, Reid MS, Nomura DK, Nissenson RA, Correa SM, Ingraham HA

Estrogen signaling in arcuate Kiss1 neurons suppresses a sex-dependent female circuit promoting dense strong bones.

Nature communications

Herber CB, Krause WC, Wang L, Bayrer JR, Li A, Schmitz M, Fields A, Ford B, Zhang Z, Reid MS, Nomura DK, Nissenson RA, Correa SM, Ingraham HA

LRH-1 mitigates intestinal inflammatory disease by maintaining epithelial homeostasis and cell survival.

Nature communications

Bayrer JR, Wang H, Nattiv R, Suzawa M, Escusa HS, Fletterick RJ, Klein OD, Moore DD, Ingraham HA

LRH-1 regulates hepatic lipid homeostasis and maintains arachidonoyl phospholipid pools critical for phospholipid diversity.

JCI insight

Miranda DA, Krause WC, Cazenave-Gassiot A, Suzawa M, Escusa H, Foo JC, Shihadih DS, Stahl A, Fitch M, Nyangau E, Hellerstein M, Wenk MR, Silver DL, Ingraham HA

Timing of adrenal regression controlled by synergistic interaction between Sf1 SUMOylation and Dax1.

Development (Cambridge, England)

Xing Y, Morohashi KI, Ingraham HA, Hammer GD

Abstract 281: Hepatic Liver Receptor Homolog-1, a Key Regulator of Lipid Storage and Phospholipid Diversity.

Circulation research

Diego A Miranda, William C Krause, Amaury Cazenave, Hazel A Escusa, Diyala S Shihadih, Andreas Stahl, Markus R Wenk, David L Silver, Holly A Ingraham

Enterochromaffin Cells Are Gut Chemosensors that Couple to Sensory Neural Pathways.

Cell

Bellono NW, Bayrer JR, Leitch DB, Castro J, Zhang C, O'Donnell TA, Brierley SM, Ingraham HA, Julius D

Disulfide-Trapping Identifies a New, Effective Chemical Probe for Activating the Nuclear Receptor Human LRH-1 (NR5A2).

PloS one

de Jesus Cortez F, Suzawa M, Irvy S, Bruning JM, Sablin E, Jacobson MP, Fletterick RJ, Ingraham HA, England PM

A gene-expression screen identifies a non-toxic sumoylation inhibitor that mimics SUMO-less human LRH-1 in liver.

eLife

Suzawa M, Miranda DA, Ramos KA, Ang KK, Faivre EJ, Wilson CG, Caboni L, Arkin MR, Kim YS, Fletterick RJ, Diaz A, Schneekloth JS, Ingraham HA

Structure of Liver Receptor Homolog-1 (NR5A2) with PIP3 hormone bound in the ligand binding pocket.

Journal of structural biology

Sablin EP, Blind RD, Uthayaruban R, Chiu HJ, Deacon AM, Das D, Ingraham HA, Fletterick RJ

Sex-dependent changes in metabolism and behavior, as well as reduced anxiety after eliminating ventromedial hypothalamus excitatory output.

Molecular metabolism

Cheung CC, Krause WC, Edwards RH, Yang CF, Shah NM, Hnasko TS, Ingraham HA

The Signaling Phospholipid PIP3 Functions As a Ligand Hormone For Nuclear Receptors.

The FASEB Journal

Holly Ingraham, Raymond Blind, Elena Sablin, Debanu Das, Robert Fletterick

An estrogen-responsive module in the ventromedial hypothalamus selectively drives sex-specific activity in females.

Cell reports

Correa SM, Newstrom DW, Warne JP, Flandin P, Cheung CC, Lin-Moore AT, Pierce AA, Xu AW, Rubenstein JL, Ingraham HA

The signaling phospholipid PIP3 creates a new interaction surface on the nuclear receptor SF-1.

Proceedings of the National Academy of Sciences of the United States of America

Blind RD, Sablin EP, Kuchenbecker KM, Chiu HJ, Deacon AM, Das D, Fletterick RJ, Ingraham HA

Science Signaling Podcast: 19 June 2012.

Science signaling

H. A. Ingraham, R. D. Blind, A. M. VanHook

An affective disorder in zebrafish with mutation of the glucocorticoid receptor.

Molecular psychiatry

Ziv L, Muto A, Schoonheim PJ, Meijsing SH, Strasser D, Ingraham HA, Schaaf MJ, Yamamoto KR, Baier H

Eliminating SF-1 (NR5A1) sumoylation in vivo results in ectopic hedgehog signaling and disruption of endocrine development.

Developmental cell

Lee FY, Faivre EJ, Suzawa M, Lontok E, Ebert D, Cai F, Belsham DD, Ingraham HA

Demasculinization and feminization of male gonads by atrazine: consistent effects across vertebrate classes.

The Journal of steroid biochemistry and molecular biology

Hayes TB, Anderson LL, Beasley VR, de Solla SR, Iguchi T, Ingraham H, Kestemont P, Kniewald J, Kniewald Z, Langlois VS, Luque EH, McCoy KA, Muñoz-de-Toro M, Oka T, Oliveira CA, Orton F, Ruby S, Suzawa M, Tavera-Mendoza LE, Trudeau VL, Victor-Costa AB, Willingham E

Small molecule agonists of the orphan nuclear receptors steroidogenic factor-1 (SF-1, NR5A1) and liver receptor homologue-1 (LRH-1, NR5A2).

Journal of medicinal chemistry

Whitby RJ, Stec J, Blind RD, Dixon S, Leesnitzer LM, Orband-Miller LA, Williams SP, Willson TM, Xu R, Zuercher WJ, Cai F, Ingraham HA

Hypothalamic Fetal Programming of Energy Homeostasis.

Obesity Before Birth

Clement C. Cheung, Holly A. Ingraham

Molecular pathways controlling development of thalamus and hypothalamus: from neural specification to circuit formation.

The Journal of neuroscience : the official journal of the Society for Neuroscience

Blackshaw S, Scholpp S, Placzek M, Ingraham H, Simerly R, Shimogori T

Regulation of C. elegans fat uptake and storage by acyl-CoA synthase-3 is dependent on NR5A family nuclear hormone receptor nhr-25.

Cell metabolism

Mullaney BC, Blind RD, Lemieux GA, Perez CL, Elle IC, Faergeman NJ, Van Gilst MR, Ingraham HA, Ashrafi K

Stimulating the GPR30 estrogen receptor with a novel tamoxifen analogue activates SF-1 and promotes endometrial cell proliferation.

Cancer research

Lin BC, Suzawa M, Blind RD, Tobias SC, Bulun SE, Scanlan TS, Ingraham HA

The structure of corepressor Dax-1 bound to its target nuclear receptor LRH-1.

Proceedings of the National Academy of Sciences of the United States of America

Sablin EP, Woods A, Krylova IN, Hwang P, Ingraham HA, Fletterick RJ

Structure of SF-1 bound by different phospholipids: evidence for regulatory ligands.

Molecular endocrinology (Baltimore, Md.)

Sablin EP, Blind RD, Krylova IN, Ingraham JG, Cai F, Williams JD, Fletterick RJ, Ingraham HA

Decreased recognition of SUMO-sensitive target genes following modification of SF-1 (NR5A1).

Molecular and cellular biology

Campbell LA, Faivre EJ, Show MD, Ingraham JG, Flinders J, Gross JD, Ingraham HA

Nuclear Receptors, Chemistry of.

Wiley Encyclopedia of Chemical Biology

Lioudmila A. Campbell, Holly A. Ingraham

The neonatal ventromedial hypothalamus transcriptome reveals novel markers with spatially distinct patterning.

The Journal of neuroscience : the official journal of the Society for Neuroscience

Kurrasch DM, Cheung CC, Lee FY, Tran PV, Hata K, Ingraham HA

International Union of Pharmacology. LXVI. Orphan nuclear receptors.

Pharmacological reviews

Benoit G, Cooney A, Giguere V, Ingraham H, Lazar M, Muscat G, Perlmann T, Renaud JP, Schwabe J, Sladek F, Tsai MJ, Laudet V

Diminished hypothalamic bdnf expression and impaired VMH function are associated with reduced SF-1 gene dosage.

The Journal of comparative neurology

Tran PV, Akana SF, Malkovska I, Dallman MF, Parada LF, Ingraham HA

Orphan nuclear receptors adopted by crystallography.

Current opinion in structural biology

Ingraham HA, Redinbo MR

The DEAD-box protein DP103 (Ddx20 or Gemin-3) represses orphan nuclear receptor activity via SUMO modification.

Molecular and cellular biology

Lee MB, Lebedeva LA, Suzawa M, Wadekar SA, Desclozeaux M, Ingraham HA

Structural analyses reveal phosphatidyl inositols as ligands for the NR5 orphan receptors SF-1 and LRH-1.

Cell

Krylova IN, Sablin EP, Moore J, Xu RX, Waitt GM, MacKay JA, Juzumiene D, Bynum JM, Madauss K, Montana V, Lebedeva L, Suzawa M, Williams JD, Williams SP, Guy RK, Thornton JW, Fletterick RJ, Willson TM, Ingraham HA

128 UPREGULATION OF WNT4 DISRUPTS TESTICULAR VASCULOGENESIS AND INHIBITS TESTOSTERONE SYNTHESIS.

Journal of Investigative Medicine

E. Vilain, J.H.-C. Shen, R. Olaso, H. A. Ingraham, B. K. Jordan

UPREGULATION OF WNT4 DISRUPTS TESTICULAR VASCULOGENESIS AND INHIBITS TESTOSTERONE SYNTHESIS.: 128.

Journal of Investigative Medicine

E. Vilain, J.H.-C. Shen, R. Olaso, H. A. Ingraham, B. K. Jordan

Wnt4 overexpression disrupts normal testicular vasculature and inhibits testosterone synthesis by repressing steroidogenic factor 1/beta-catenin synergy.

Proceedings of the National Academy of Sciences of the United States of America

Jordan BK, Shen JH, Olaso R, Ingraham HA, Vilain E

Structural basis for ligand-independent activation of the orphan nuclear receptor LRH-1.

Molecular cell

Sablin EP, Krylova IN, Fletterick RJ, Ingraham HA

Tissue growth and remodeling of the embryonic and adult adrenal gland.

Annals of the New York Academy of Sciences

Bland ML, Desclozeaux M, Ingraham HA

Requirement of the orphan nuclear receptor SF-1 in terminal differentiation of ventromedial hypothalamic neurons.

Molecular and cellular neurosciences

Tran PV, Lee MB, Marín O, Xu B, Jones KR, Reichardt LF, Rubenstein JR, Ingraham HA

Thyroid hormone receptor-beta mutations conferring hormone resistance and reduced corepressor release exhibit decreased stability in the N-terminal ligand-binding domain.

Molecular endocrinology (Baltimore, Md.)

Huber BR, Desclozeaux M, West BL, Cunha-Lima ST, Nguyen HT, Baxter JD, Ingraham HA, Fletterick RJ

Phosphorylation and intramolecular stabilization of the ligand binding domain in the nuclear receptor steroidogenic factor 1.

Molecular and cellular biology

Desclozeaux M, Krylova IN, Horn F, Fletterick RJ, Ingraham HA

Anti-Müllerian hormone inhibits initiation of primordial follicle growth in the mouse ovary.

Endocrinology

Durlinger AL, Gruijters MJ, Kramer P, Karels B, Ingraham HA, Nachtigal MW, Uilenbroek JT, Grootegoed JA, Themmen AP

Involvement of a matrix metalloproteinase in MIS-induced cell death during urogenital development.

Development (Cambridge, England)

Roberts LM, Visser JA, Ingraham HA

Regulation of the orphan nuclear receptor steroidogenic factor 1 by Sox proteins.

Molecular endocrinology (Baltimore, Md.)

Shen JH, Ingraham HA

The serine/threonine transmembrane receptor ALK2 mediates Müllerian inhibiting substance signaling.

Molecular endocrinology (Baltimore, Md.)

Visser JA, Olaso R, Verhoef-Post M, Kramer P, Themmen AP, Ingraham HA

Müllerian inhibitory substance induces growth of rat preantral ovarian follicles.

Biology of reproduction

McGee EA, Smith R, Spears N, Nachtigal MW, Ingraham H, Hsueh AJ

Haploinsufficiency of steroidogenic factor-1 in mice disrupts adrenal development leading to an impaired stress response.

Proceedings of the National Academy of Sciences of the United States of America

Bland ML, Jamieson CA, Akana SF, Bornstein SR, Eisenhofer G, Dallman MF, Ingraham HA

Gene dosage effects of steroidogenic factor 1 (SF-1) in adrenal development and the stress.

Endocrine research

Bland ML, Jamieson C, Akana S, Dallman M, Ingraham HA

SF-1 and DAX-1: A Dynamic Duo in Endocrine Development Mark W. Nachtigal,.

Gene Engineering in Endocrinology

Debra Enyeart-VanHouten, Holly A. Ingraham

Autocrine and paracrine Müllerian inhibiting substance hormone signaling in reproduction.

Recent progress in hormone research

Ingraham HA, Hirokawa Y, Roberts LM, Mellon SH, McGee E, Nachtigal MW, Visser JA

SF-1 and DAX-1.

Gene Engineering in Endocrinology

Mark W. Nachtigal, Debra Enyeart-VanHouten, Holly A. Ingraham

New solutions to an ancient riddle: defining the differences between Adam and Eve.

American journal of human genetics

Roberts LM, Shen J, Ingraham HA

Steroidogenic factor-1: its role in endocrine organ development and differentiation.

Frontiers in neuroendocrinology

Hammer GD, Ingraham HA

Paracrine-mediated apoptosis in reproductive tract development.

Developmental biology

Roberts LM, Hirokawa Y, Nachtigal MW, Ingraham HA

Phosphorylation of the nuclear receptor SF-1 modulates cofactor recruitment: integration of hormone signaling in reproduction and stress.

Molecular cell

Hammer GD, Krylova I, Zhang Y, Darimont BD, Simpson K, Weigel NL, Ingraham HA

Neuronal expression of the 5HT3 serotonin receptor gene requires nuclear factor 1 complexes.

The Journal of neuroscience : the official journal of the Society for Neuroscience

Bedford FK, Julius D, Ingraham HA

Wilms' tumor 1 and Dax-1 modulate the orphan nuclear receptor SF-1 in sex-specific gene expression.

Cell

Nachtigal MW, Hirokawa Y, Enyeart-VanHouten DL, Flanagan JN, Hammer GD, Ingraham HA

Bioactivation of Müllerian inhibiting substance during gonadal development by a kex2/subtilisin-like endoprotease.

Proceedings of the National Academy of Sciences of the United States of America

Nachtigal MW, Ingraham HA

Molecular biology of pituitary development and disease.

Hormone research

Bedford FK, Christopherson K, Nachtigal MW, Shen WH, Julius DJ, Ingraham HA

The nuclear receptor steroidogenic factor 1 acts at multiple levels of the reproductive axis.

Genes & development

Ingraham HA, Lala DS, Ikeda Y, Luo X, Shen WH, Nachtigal MW, Abbud R, Nilson JH, Parker KL

Developmental expression of mouse steroidogenic factor-1, an essential regulator of the steroid hydroxylases.

Molecular endocrinology (Baltimore, Md.)

Ikeda Y, Shen WH, Ingraham HA, Parker KL

Mutation of the POU-specific domain of Pit-1 and hypopituitarism without pituitary hypoplasia.

Science (New York, N.Y.)

Pfäffle RW, DiMattia GE, Parks JS, Brown MR, Wit JM, Jansen M, Van der Nat H, Van den Brande JL, Rosenfeld MG, Ingraham HA

Autoregulation of pit-1 gene expression mediated by two cis-active promoter elements.

Nature

Chen RP, Ingraham HA, Treacy MN, Albert VR, Wilson L, Rosenfeld MG

Pituitary cell phenotypes involve cell-specific Pit-1 mRNA translation and synergistic interactions with other classes of transcription factors.

Genes & development

Simmons DM, Voss JW, Ingraham HA, Holloway JM, Broide RS, Rosenfeld MG, Swanson LW

A family of POU-domain and Pit-1 tissue-specific transcription factors in pituitary and neuroendocrine development.

Annual review of physiology

Ingraham HA, Albert VR, Chen RP, Crenshaw 3d EB, Elsholtz HP, He X, Kapiloff MS, Mangalam HJ, Swanson LW, Treacy MN

Expression of a large family of POU-domain regulatory genes in mammalian brain development.

Nature

He X, Treacy MN, Simmons DM, Ingraham HA, Swanson LW, Rosenfeld MG

A pituitary POU domain protein, Pit-1, activates both growth hormone and prolactin promoters transcriptionally.

Genes & development

Mangalam HJ, Albert VR, Ingraham HA, Kapiloff M, Wilson L, Nelson C, Elsholtz H, Rosenfeld MG

The POU domain: a large conserved region in the mammalian pit-1, oct-1, oct-2, and Caenorhabditis elegans unc-86 gene products.

Genes & development

Herr W, Sturm RA, Clerc RG, Corcoran LM, Baltimore D, Sharp PA, Ingraham HA, Rosenfeld MG, Finney M, Ruvkun G

A tissue-specific transcription factor containing a homeodomain specifies a pituitary phenotype.

Cell

Ingraham HA, Chen RP, Mangalam HJ, Elsholtz HP, Flynn SE, Lin CR, Simmons DM, Swanson L, Rosenfeld MG

Role of intrinsic protein tyrosine kinase in function and metabolism of the epidermal growth factor receptor.

Cold Spring Harbor symposia on quantitative biology

Gill GN, Chen WS, Lazar CS, Glenney JR, Wiley HS, Ingraham HA, Rosenfeld MG

The mouse Thy-1.2 glycoprotein gene: complete sequence and identification of an unusual promoter.

Journal of immunology (Baltimore, Md. : 1950)

Ingraham HA, Lawless GM, Evans GA

Mechanism of thymineless death.

Advances in experimental medicine and biology

Goulian M, Bleile BM, Dickey LM, Grafstrom RH, Ingraham HA, Neynaber SA, Peterson MS, Tseng BY

Expression of the Thy-1 glycoprotein gene by DNA-mediated gene transfer.

Proceedings of the National Academy of Sciences of the United States of America

Evans GA, Ingraham HA, Lewis K, Cunningham K, Seki T, Moriuchi T, Chang HC, Silver J, Hyman R

Mechanism for exclusion of 5-fluorouracil from DNA.

Cancer research

Ingraham HA, Tseng BY, Goulian M

Characterization of the association of specific proteins with messenger ribonucleic acid.

Biochemistry

Barrieux A, Ingraham HA, Nystul S, Rosenfeld MG