Heddwen L Brooks

Heddwen L Brooks

Professor, Physiology
Professor, Medicine
Professor, Biomedical Engineering
Professor, Physiological Sciences - GIDP
Associate Professor, Pharmacology
Professor, BIO5 Institute
Primary Department
Department Affiliations
(520) 626-7702

Research Interest

Dr. Brooks is a renal physiologist and has developed microarray technology to address in vivo signaling pathways involved in the hormonal regulation of renal function. Current areas of research in the Brooks Laboratory are focused on importance of sex differences in the onset of postmenopausal hypertension and diabetic kidney disease and identifying new therapies for polycystic kidney disease and lithium-induced nephropathy.


Kusne, Y., Goldberg, E. L., Parker, S. S., Hapak, S. M., Maskaykina, I. Y., Chew, W. M., Limesand, K. H., Brooks, H. L., Price, T. J., Sanai, N., Nikolich-Zugich, J., & Ghosh, S. (2014). Contrasting effects of chronic, systemic treatment with mTOR inhibitors rapamycin and metformin on adult neural progenitors in mice. Age (Dordrecht, Netherlands), 36(1), 199-212.

The chronic and systemic administration of rapamycin extends life span in mammals. Rapamycin is a pharmacological inhibitor of mTOR. Metformin also inhibits mTOR signaling but by activating the upstream kinase AMPK. Here we report the effects of chronic and systemic administration of the two mTOR inhibitors, rapamycin and metformin, on adult neural stem cells of the subventricular region and the dendate gyrus of the mouse hippocampus. While rapamycin decreased the number of neural progenitors, metformin-mediated inhibition of mTOR had no such effect. Adult-born neurons are considered important for cognitive and behavioral health, and may contribute to improved health span. Our results demonstrate that distinct approaches of inhibiting mTOR signaling can have significantly different effects on organ function. These results underscore the importance of screening individual mTOR inhibitors on different organs and physiological processes for potential adverse effects that may compromise health span.

Rivera, Z., Christian, P. J., Marion, S. L., Brooks, H. L., & Hoyer, P. B. (2009). Steroidogenic capacity of residual ovarian tissue in 4-vinylcyclohexene diepoxide-treated mice. Biology of reproduction, 80(2), 328-36.
BIO5 Collaborators
Heddwen L Brooks, Zelieann R Craig

Menopause is an important public health issue because of its association with a number of disorders. Androgens produced by residual ovarian tissue after menopause could impact the development of these disorders. It has been unclear, however, whether the postmenopausal ovary retains steroidogenic capacity. Thus, an ovary-intact mouse model for menopause that uses the occupational chemical 4-vinylcyclohexene diepoxide (VCD) was used to characterize the expression of steroidogenic genes in residual ovarian tissue of follicle-depleted mice. Female B6C3F1 mice (age, 28 days) were dosed daily for 20 days with either vehicle or VCD (160 mg kg(-1) day(-1)) to induce ovarian failure. Ovaries were collected on Day 181 and analyzed for mRNA and protein. Acyclic aged mice were used as controls for natural ovarian senescence. Relative to cycling controls, expression of mRNA encoding steroidogenic acute regulatory protein (Star); cholesterol side-chain cleavage (Cyp11a1); 3beta-hydroxysteroid dehydrogenase (Hsd3b); 17alpha-hydroxylase (Cyp17a1); scavenger receptor class B, type 1 (Scarb1); low-density lipoprotein receptor (Ldlr); and luteinizing hormone receptor (Lhcgr) was enriched in VCD-treated ovaries. In acyclic aged ovaries, mRNA expression for only Cyp17a1 and Lhcgr was greater than that in controls. Compared to cycling controls, ovaries from VCD-treated and aged mice had similar levels of HSD3B, CYP17A1, and LHCGR protein. The pattern of protein immunofluorescence staining for HSD3B in follicle-depleted (VCD-treated) ovaries was homogeneous, whereas that for CYP17A1 was only seen in residual interstitial cells. Circulating levels of FSH and LH were increased, and androstenedione levels were detectable following follicle depletion in VCD-treated mice. These findings support the idea that residual ovarian tissue in VCD-treated mice retains androgenic capacity.

Walker, R. J., Brooks, H. L., & Holden-Dye, L. (1996). Evolution and overview of classical transmitter molecules and their receptors. Parasitology, 113 Suppl, S3-33.

All the classical transmitter ligand molecules evolved at least 1000 million years ago. With the possible exception of the Porifera and coelenterates (Cnidaria), they occur in all the remaining phyla. All transmitters have evolved the ability to activate a range of ion channels, resulting in excitation, inhibition and biphasic or multiphasic responses. All transmitters can be synthesised in all three basic types of neurones, i.e. sensory, interneurone and motoneurone. However their relative importance as sensory, interneurone or motor transmitters varies widely between the phyla. It is likely that all neurones contain more than one type of releasable molecule, often a combination of a classical transmitter and a neuroactive peptide. Second messengers, i.e. G proteins and phospholipase C systems, appeared early in evolution and occur in all phyla that have been investigated. Although the evidence is incomplete, it is likely that all the classical transmitter receptor subtypes identified in mammals, also occur throughout the phyla. The invertebrate receptors so far cloned show some interesting homologies both between those from different invertebrate phyla and with mammalian receptors. This indicates that many of the basic receptor subtypes, including benzodiazepine subunits, evolved at an early period, probably at least 800 million years ago. Overall, the evidence stresses the similarity between the major phyla rather than their differences, supporting a common origin from primitive helminth stock.

Anthony, T. L., Brooks, H. L., Boassa, D., Leonov, S., Yanochko, G. M., Regan, J. W., & Yool, A. J. (2000). Cloned human aquaporin-1 is a cyclic GMP-gated ion channel. Molecular pharmacology, 57(3), 576-88.

Aquaporin-1 (AQP1) is a member of the membrane intrinsic protein (MIP) gene family and is known to provide pathways for water flux across cell membranes. We show here that cloned human AQP1 not only mediates water flux but also serves as a cGMP-gated ion channel. Two-electrode voltage-clamp analyses showed consistent activation of an ionic conductance in wild-type AQP1-expressing oocytes after the direct injection of cGMP (50 nl of 100 mM). Current activation was not observed in control (water-injected) oocytes or in AQP5-expressing oocytes with osmotic water permeabilities equivalent to those seen with AQP1. Patch-clamp recordings revealed large conductance channels (150 pS in K(+) saline) in excised patches from AQP1-expressing oocytes after the application of cGMP to the internal side. Amino acid sequence alignments between AQP1 and sensory cyclic-nucleotide-gated channels showed similarities between the cyclic-nucleotide-gated binding domain and the AQP1 carboxyl terminus that were not present in AQP5. Competitive radioligand-binding assays with [(3)H]cGMP demonstrated specific binding (K(D) = 0.2 microM) in AQP1-expressing Sf9 cells but not in controls. These results indicate that AQP1 channels have the capacity to participate in ionic signaling after the activation of cGMP second-messenger pathways.

Greer, K. A., McReynolds, M. R., Brooks, H. L., & Hoying, J. B. (2006). CARMA: A platform for analyzing microarray datasets that incorporate replicate measures. BMC bioinformatics, 7, 149.

The incorporation of statistical models that account for experimental variability provides a necessary framework for the interpretation of microarray data. A robust experimental design coupled with an analysis of variance (ANOVA) incorporating a model that accounts for known sources of experimental variability can significantly improve the determination of differences in gene expression and estimations of their significance.