Originally from Panama City, Florida, I graduated from Florida State University with a BS in Sociology and Psychology. I then completed my Phd in Neuroscience under the mentorship of Dr. Karen Berkley at Florida State University. During my graduate career my primary research focus involved investigating peripheral contributors to endometriosis-associated vaginal hyperalgesia (increased pain from a stimulus that normally provokes pain) in a rat model of endometriosis. To do this, I incorporated a unique method of behavioral psychophysics to assess changes in vaginal nociception (the neural process of encoding noxious stimuli), immunohistochemistry, and mass spectrometry. Specifically, my PhD dissertation examined the roll of endometrial cyst innervation, vaginal innervation, and prostaglandins in endometriosis-induced vaginal hyperalgesia in the rat model.
I joined the Stanford department of Anesthesiology, Perioperative Pain and Medicine as a National Institute of General Medicine (NIGMS) T32 postdoctoral trainee in 2015. Towards the end of this two year training period, I applied for and was awarded a K99 Pathway to Independence Award by the National Institute of Child Health and Human Development (NICHD). For this award (100% effort), I am targeting reactive aldehyde metabolism as a treatment strategy and diagnostic biomarker for endometriosis and its associated pain.
Some of my continued research interests and projects stemming from my time in Dr. Karen Berkley’s lab include the involvement of the endocannabinoid system in endometriosis and its associated pain, the influence of reproductive status and menstrual/estrous stage on pain, and sex differences in pain.
Outside of research my primary focus, enjoyment, and purpose in life is being an amazing mother to my little girl Alexis!
Instructor, Anesthesiology, Perioperative and Pain Medicine
Honors & Awards
NIH Pathway to Independence Award (K99), National Institute of Child Health and Human Development (NICHD) (2017)
NIH Institutional Postdoctoral Anesthesia Training Grant in Biomedical Research (T32), National Institute of General Medicine Sciences (NIGMS) (2015-2017)
North American Pain School Class of 2017, Educational Initiative of IASP and ACTTION (2017)
Research Award Grant, Endometriosis Foundation of America (2017)
Seed Grant, Stanford Women in Sex Differences and Medicine (WSDM) (2015)
Helena Anna Henzl-Gabor Women in Science Fellowship for Postdoctoral Scholars, Stanford University (2015, 2017)
Lloyd M. Beidler Neuroscience Graduate Research Scholar Award, Florida State University (2012)
Bryan Robinson Endowment for the Neurosciences, Tallahassee Memorial HealthCare (2011)
South East Nerve Conference Grant, National Science Foundation (NSF) (2011)
Boards, Advisory Committees, Professional Organizations
Member, Society for Neuroscience (SfN) (2004 - Present)
Member, Society of Behavioral Neuroendocrinology (SBN) (2006 - Present)
Member, Association for Women in Science (AWIS) (2009 - Present)
Member, International Association for the Study of Pain (IASP) (2014 - Present)
Member, American Pain Society (APS) (2015 - Present)
Member, Academy of Women’s Health (AWH) (2015 - Present)
Member, World Endometriosis Society (WES) (2015 - Present)
Member, American Society for Reproductive Medicine (ASRM), EndoSIG (Endometriosis Special Interest Group) (2015 - Present)
Member, European Society of Human Reproduction and Embryology (ESHRE) (2015 - Present)
Member, American Society for Pharmacological and Experimental Therapeutics (ASPET) (2015 - Present)
Member, American Physiological Society (APS) (2018 - Present)
Doctor of Philosophy, Florida State University, Nueroscience (2014)
Community and International Work
Women in Science and Engineering (WISE)
Opportunities for Student Involvement
Current Research and Scholarly Interests
Endometriosis is one of the few disorders in women's health research with little progress made in the last 20 years relative to screening, detection, prognosis, and treatment. Reactive aldehydes, formed during oxidative stress, are produced and elevated in women with endometriosis and are metabolized intracellularly by aldehyde dehydrogenase 2 (ALDH2). My K99/R00 central hypothesis is that the balance of reactive aldehyde production and metabolism underlies endometriosis and endometriosis-associated pain. My research goal of this project is to determine the role of reactive aldehyde production and aldehyde metabolism in endometriosis to identify a novel treatment and biomarker for women suffering from endometriosis.
During the K99 phase (Years 1-2): Aim 1 will determine if reactive aldehyde metabolism influences the development of endometriosis using ALDH2*2 knock-in mice with reduced aldehyde metabolism, an experimental model of endometriosis, and cutting-edge techniques to measure reactive aldehyde production and aldehyde metabolism. Aim 2 will determine if reactive aldehyde metabolism is altered in women with endometriosis using techniques from Aim 1 to analyze human endometrial tissue samples from Caucasian and Asian (*2 variants) women with and without endometriosis provided by the UCSF NIH Human Endometrial Tissue Bank. During the R00 phase (Years 3-5): Aim 3 will determine if reactive aldehyde metabolism influences endometriosis-associated primary abdominal and secondary vaginal pain (hyperalgesia) using an endometriosis experimental model, unique equipment and specialized skills to assess hyperalgesia, and a novel ALDH2 activator (to increase reactive aldehyde metabolism).
Overall, my research will advance the knowledge of how reactive aldehyde production and metabolism contribute to endometriosis development and its associated pain. If my hypothesis is found to be true, my research findings will potentially provide a therapeutic and diagnostic biomarker to reduce the years of unnecessary suffering for the 176 million women world-wide with endometriosis.
Prostaglandin levels, vaginal innervation, and cyst innervation as peripheral contributors to endometriosis-associated vaginal hyperalgesia in rodents.
Molecular and cellular endocrinology
2016; 437: 120-129
Endometriosis is a painful condition characterized by growth of endometrial cysts outside the uterus. Here, we tested the hypothesis that peripheral innervation and prostaglandin levels contribute to endometriosis-associated pain. Female Sprague-Dawley rats (n = 16) were surgically instrumented by transplanting uterine tissue onto mesenteric arteries within the peritoneal cavity to create a model of endometriosis which forms extra-uterine endometrial cysts and vaginal hyperalgesia. Our results describe a significant positive correlation between endometriosis-induced vaginal hyperalgesia and cyst innervation density (sensory, r = 0.70, p = 0.003; sympathetic, r = 0.55, p = 0.03), vaginal canal sympathetic innervation density (r = 0.80, p = 0.003), and peritoneal fluid levels of the prostaglandins PGE2 (r = 0.65, p = 0.01) and PGF2α (r = 0.63, p = 0.02). These results support the involvement of cyst innervation and prostaglandins in endometriosis-associated pain. We also describe how sympathetic innervation density of the vaginal canal is an important predictor of vaginal hyperalgesia.
View details for DOI 10.1016/j.mce.2016.08.017
View details for PubMedID 27524411
Developing precision medicine for people of East Asian descent
JOURNAL OF BIOMEDICAL SCIENCE
The goal of precision medicine is to separate patient populations into groups to ultimately provide customized care tailored to patients. In terms of precision medicine, ~540 million people in the world have a genetic variant of the aldehyde dehydrogenase 2 (ALDH2) enzyme causing a flushing response and tachycardia after alcohol consumption. The genetic variant is identified as ALDH2*2 and originates from East Asian descendants of the Han Chinese. The variant is particularly important to consider when discussing lifestyle choices with patients in terms of risk for developing specific diseases, preventative screening, and selection of medications for treatment. Here we provide examples why patients with an ALDH2*2 variant need more individualized medical management which is becoming a more standard practice in the precision medicine era.
View details for DOI 10.1186/s12929-016-0299-3
View details for Web of Science ID 000387622600001
View details for PubMedID 27835996
View details for PubMedCentralID PMC5106841
Transient Receptor Potential Ankyrin 1 Activation within the Cardiac Myocyte Limits Ischemia-reperfusion Injury in Rodents.
Recent evidence suggests that cross talk exists between cellular pathways important for pain signaling and ischemia-reperfusion injury. Here, the authors address whether the transient receptor potential ankyrin 1 (TRPA1) channel, important in pain signaling, is present in cardiac myocytes and regulates cardiac ischemia-reperfusion injury.For biochemical analysis of TRPA1, techniques including quantitative polymerase chain reaction, Western blot, and immunofluorescence were used. To determine how TRPA1 mediates cellular injury, the authors used an in vivo model of rat cardiac ischemia-reperfusion injury and adult rat-isolated cardiac myocytes subjected to hypoxia-reoxygenation.The authors' biochemical analysis indicates that TRPA1 is within the cardiac myocytes. Further, using a rat in vivo model of cardiac injury, the TRPA1 activators ASP 7663 and optovin reduce myocardial injury (45 ± 5%* and 44 ± 8%,* respectively, vs. control, 66 ± 6% infarct size/area at risk; n = 6 per group; mean ± SD; *P < 0.001). TRPA1 inhibition also blocked the infarct size-sparing effects of morphine. In isolated cardiac myocytes, the TRPA1 activators ASP 7663 and optovin reduce cardiac myocyte cell death when given during reoxygenation (20 ± 3%* and 22 ± 4%* vs. 36 ± 3%; percentage of dead cells per field, n = 6 per group; mean ± SD; *P < 0.05). For a rat in vivo model of cardiac injury, the infarct size-sparing effect of TRPA1 activators also occurs during reperfusion.The authors' data suggest that TRPA1 is present within the cardiac myocytes and is important in regulating myocardial reperfusion injury. The presence of TRPA1 within the cardiac myocytes may potentially explain why certain pain relievers that can block TRPA1 activation, such as cyclooxygenase-2 inhibitors or some nonsteroidal antiinflammatory drugs, could be associated with cardiovascular risk.
View details for PubMedID 27748654
View details for PubMedCentralID PMC5110384
Sprouted Innervation into Uterine Transplants Contributes to the Development of Hyperalgesia in a Rat Model of Endometriosis
2012; 7 (2)
Endometriosis is an enigmatic painful disorder whose pain symptoms remain difficult to alleviate in large part because the disorder is defined by extrauteral endometrial growths whose contribution to pain is poorly understood. A rat model (ENDO) involves autotransplanting on abdominal arteries uterine segments that grow into vascularized cysts that become innervated with sensory and sympathetic fibers. ENDO rats exhibit vaginal hyperalgesia. We used behavioral, physiological, and immunohistochemical methods to test the hypothesis that cyst innervation contributes to the development of this hyperalgesia after transplant. Rudimentary sensory and sympathetic innervation appeared in the cysts at two weeks, sprouted further and more densely into the cyst wall by four weeks, and matured by six weeks post-transplant. Sensory fibers became abnormally functionally active between two and three weeks post-transplant, remaining active thereafter. Vaginal hyperalgesia became significant between four and five weeks post-transplant, and stabilized after six to eight weeks. Removing cysts before they acquired functional innervation prevented vaginal hyperalgesia from developing, whereas sham cyst removal did not. Thus, abnormally-active innervation of ectopic growths occurs before hyperalgesia develops, supporting the hypothesis. These findings suggest that painful endometriosis can be classified as a mixed inflammatory/neuropathic pain condition, which opens new avenues for pain relief. The findings also have implications beyond endometriosis by suggesting that functionality of any transplanted tissue can be influenced by the innervation it acquires.
View details for DOI 10.1371/journal.pone.0031758
View details for Web of Science ID 000302873700093
View details for PubMedID 22363725
- Don't dismiss dysmenorrhea! PAIN 2011; 152 (9): 1940-1941
Endocannabinoid involvement in endometriosis
2010; 151 (3): 703-710
Endometriosis is a disease common in women that is defined by abnormal extrauteral growths of uterine endometrial tissue and associated with severe pain. Partly because how the abnormal growths become associated with pain is poorly understood, the pain is difficult to alleviate without resorting to hormones or surgery, which often produce intolerable side effects or fail to help. Recent studies in a rat model and women showed that sensory and sympathetic nerve fibers sprout branches to innervate the abnormal growths. This situation, together with knowledge that the endocannabinoid system is involved in uterine function and dysfunction and that exogenous cannabinoids were once used to alleviate endometriosis-associated pain, suggests that the endocannabinoid system is involved in both endometriosis and its associated pain. Herein, using a rat model, we found that CB1 cannabinoid receptors are expressed on both the somata and fibers of both the sensory and sympathetic neurons that innervate endometriosis's abnormal growths. We further found that CB1 receptor agonists decrease, whereas CB1 receptor antagonists increase, endometriosis-associated hyperalgesia. Together these findings suggest that the endocannabinoid system contributes to mechanisms underlying both the peripheral innervation of the abnormal growths and the pain associated with endometriosis, thereby providing a novel approach for the development of badly-needed new treatments.
View details for DOI 10.1016/j.pain.2010.08.037
View details for Web of Science ID 000283657300023
View details for PubMedID 20833475
Endometriosis-induced vaginal hyperalgesia in the rat: Role of the ectopic growths and their innervation
2009; 147 (1-3): 255-264
Endometriosis is a painful disorder defined by extrauteral endometrial growths whose contribution to pain symptoms is poorly understood. Endometriosis is created in rats by autotransplanting on abdominal arteries pieces of either uterus (ENDO), which form cysts, or fat (shamENDO), which do not form cysts. ENDO, but not shamENDO induces vaginal hyperalgesia. We tested the hypothesis that the cysts are necessary to maintain vaginal hyperalgesia by assessing the effect of surgically removing them. Complete-cyst-removal eliminated ENDO-induced vaginal hyperalgesia up to 4 months post-operatively. Sham-cyst-removal in ENDO rats, in which cysts were not removed, or partial cyst-removal increased the ENDO-induced hyperalgesia. The decreases and increases both took 3-6 weeks to develop. Changes in ENDO-induced hyperalgesia did not occur in a control group of ENDO rats who had no surgery after ENDO. In a double-surgery control group, neither shamENDO surgery nor a subsequent sham surgery that mimicked "removal" of non-existent cysts influenced vaginal nociception. In a no-surgery control group, vaginal nociception remained stable for >6 months. The increases in ENDO-induced hyperalgesia produced by the sham-cyst-removal surgery were smaller in proestrus than in other estrous stages. During the other stages (but not during proestrus), sympathetic innervation of the cysts increased. These results suggest that maintenance of ENDO-induced vaginal hyperalgesia requires continued presence of at least some ectopic endometrial tissue, and that surgical treatment that fails to remove ectopic endometrial tissue can exacerbate the hyperalgesia, possibly due in part to an increase in the cysts' sympathetic innervation.
View details for DOI 10.1016/j.pain.2009.09.022
View details for Web of Science ID 000272612700040
View details for PubMedID 19819623
Endometriosis-induced vaginal hyperalgesia in the rat: Effect of estropause, ovariectomy, and estradiol replacement
2007; 132: S150-S159
Endometriosis (ENDO) is a painful disorder defined by extrauteral endometrial growths. It is created in rats by autotransplanting pieces of uterus (which form cysts), or, for shamENDO, fat (no cysts). ENDO induces vaginal hyperalgesia, likely via central sensitization. The severity of this hyperalgesia correlates with estradiol levels during the estrous cycle, suggesting the hyperalgesia is estradiol-modulated. If so, then hyperalgesic severity should track estradiol changes during reproductive senescence (estropause) when estradiol levels initially decrease, then increase. Using psychophysical methods to assess vaginal nociception, we found that the severity of ENDO-induced hyperalgesia paralleled estradiol changes during estropause: hyperalgesia first decreased, then returned. Furthermore, the return occurred regardless of the presence of the cysts (excised in some rats). This finding provides further support for ENDO's likely centrally-mediated effects. Additionally, the results suggest that elimination of estradiol via ovariectomy (OVX) should alleviate ENDO-induced hyperalgesia and estradiol replacement should restore it. However, in healthy and shamENDO rats, OVX produces a vaginal hyperalgesia that is alleviated by estradiol, likely via estradiol's peripheral influences on the vagina. Hence, we tested the hypothesis that OVX in ENDO rats would trigger a different type of vaginal hyperalgesia dependent on the loss of estradiol. We predicted that the opposing influences of estradiol on ENDO- and OVX-induced hyperalgesia would cancel each other. As predicted, OVX had no effect on ENDO-induced hyperalgesia and estradiol replacement alleviated it. These results suggest that, in intact rats, ENDO-induced vaginal hyperalgesia is exacerbated by estradiol, and that different mechanisms underlie ENDO-induced versus OVX-induced vaginal hyperalgesia.
View details for DOI 10.1016/j.pain.2007.09.022
View details for Web of Science ID 000251673600018
View details for PubMedID 17959309