Zeynep Madak Erdogan

University of Illinois, Urbana-Champaign | UIUC · Department of Food Science and Human Nutrition

Disclosure: H. Heath: None. J. Yoo: None. S. Akter: None. A. Jain: None. V. Sharma: None. H. McGee: None. A. Soliman: None. A. Mohamed: None. A.K. Matthews: None. R. Winn: None. Z. Madak Erdogan: None. S. Kim: None. Background: Despite the lower rates and frequency of smoking, Black men experience a higher incidence of lung cancer compared to white...

Hepatocellular carcinoma (HCC), the most common liver cancer, exhibits a higher incidence in males. Here, we report that mice lacking the bile acid regulators, Farnesoid X Receptor (FXR) and Small Heterodimer Partner (SHP), recapitulate the sex difference in liver cancer risk. Since few therapeutic options are available, we focused on understanding...

Hepatocellular carcinoma (HCC), the most common liver cancer, exhibits a higher incidence in males. Here, we report that mice lacking the bile acid regulators, Farnesoid X Receptor (FXR) and Small Heterodimer Partner (SHP), recapitulate the sex difference in liver cancer risk. Since few therapeutic options are available, we focused on understanding...

Despite lower rates and intensity of smoking, Black men experience a higher incidence of lung cancer compared to white men. The racial disparity in lung cancer is particularly pronounced in Chicago, a highly segregated urban city. Neighborhood conditions, particularly social stress, may play a role in lung tumorigenesis. Preliminary studies indicat...

Cardiovascular diseases (CVD) are one of the major causes of death globally. In addition to traditional risk factors such as unhealthy lifestyles (smoking, obesity, sedentary) and genetics, common environmental exposures, including persistent environmental contaminants, may also influence cardiovascular disease risk. Per- and polyfluoroalkyl substa...

Estrogen receptors are key pathway initiators in the aggressive development of more than two-thirds of all breast cancers. Tamoxifen (TAM) is a selective estrogen receptor modulator that disables the ER pathway and inhibits the progression of ER+ breast cancer. Unfortunately, 10-40% of patients with ER+ breast cancer who were treated with TAM exper...

NAD+ is one of the most important metabolites for cellular activities, and its biosynthesis mainly occurs through the salvage pathway using the nicotinamide phosphoribosyl transferase (NAMPT) enzyme. The main nicotinamide adenine dinucleotide (NAD) consumers, poly-ADP-ribose-polymerases and sirtuins enzymes, are heavily involved in DNA repair and c...

The potential effects of poly- and perfluoroalkyl substances (PFAS) are a recently emergent human and environmental health concern. There is a consistent link between PFAS exposure and cancer, but the mechanisms are poorly understood. Although epidemiological evidence supporting PFAS exposure and cancer in general is conflicting, there is relativel...

The tumor microenvironment consists of numerous cell populations showing diverse metabolic preferences, causing metabolic heterogeneity and therapy resistance. Fulvestrant, a clinically approved selective estrogen receptor (ER) degrader, is the standard of care for ER-positive breast cancer, yet resistance has been reported among metastatic breast...

Background: Despite smoking less, Black men experience higher incidence of lung cancer compared to white men. This health disparity is even more prevalent in Black men from Chicago, suggesting local neighborhood factors impacting tumorigenesis. Preliminary data indicate that, compared to white men, Black men are more likely to reside in neighborhoo...

Approximately 70% of human breast cancers express estrogen receptor alpha (ERα), providing a potential for targeted endocrine therapy for patients. Unfortunately, 30-40% of ER+ patients still experience recurrence and metastasis, with a 5-year relative overall survival rate of just 24% for patients with metastatic disease. In our preliminary analys...

Wnt ligand WNT4 is critical in female reproductive tissue development, with WNT4 dysregulation linked to related pathologies including breast cancer (invasive lobular carcinoma, ILC) and gynecologic cancers. WNT4 signaling in these contexts is distinct from canonical Wnt signaling yet inadequately understood. We previously identified atypical intra...

Disclosure: A. Arredondo Eve: None. E. Tunc: None. D. Mehta: None. H. Erbak-Yilmaz: None. S. Volkan Emren: None. F. Akyildiz-Akcay: None. Z. Madak Erdogan: None. Cardiovascular diseases (CVD) are the number one cause of death globally. In addition to traditional risk factors such as unhealthy lifestyles (smoking, obesity, sedentary) and genetics, c...

Disclosure: A. Santaliz Casiano: None. D. Mehta: None. H. Patel: None. G. Rauscher: None. J. Kim: None. J.M. Frasor: None. K. Hoskins: None. Background: African American (AA) women in the United States have a 40% higher breast cancer mortality rate compared with Non-Hispanic White (NHW) women. The survival disparity is particularly striking among E...

Disclosure: A.N. Mogol: None. Z. Madak Erdogan: None. Endocrine therapies exploit the hormone dependencies of the cancer cells in various ways, including by targeting estrogen receptor alpha (ERα) that is expressed by approximately 70% of human breast cancers. After treatment, recurrence and metastasis are still observed in 30-40% of ER+ patients a...

Disclosure: H. Heath: None. S. Kim: None. Z. Madak Erdogan: None. Despite smoking less, Black men experience a higher incidence of lung cancer than white men. This health disparity is even more prevalent in Black men from Chicago, suggesting local neighborhood factors impacting tumorigenesis. Preliminary data found that Black men compared to white...

Disclosure: J. Yoo: None. C. Mitra: None. Y. Yue: None. A. Soliman: None. Z. Madak Erdogan: None. Metabolic heterogeneity, a concept describing distinct differences in nutrient metabolism within the cells of a healthy or diseased tissue, is a common challenge in development and cancer research. Current methods, such as histology and Magnetic Resona...

African American (AA) women in the United States have a 40% higher breast cancer mortality rate than Non-Hispanic White (NHW) women. The survival disparity is particularly striking among (estrogen receptor positive) ER⁺ breast cancer cases. The purpose of this study is to examine whether there are racial differences in metabolic pathways typically...

Purpose Despite being a standard treatment for hormone receptor (HR)-positive/human epidermal growth factor receptor-2 (HER2)-negative metastatic breast cancer (MBC), fulvestrant continues to yield a poor prognosis in breast cancer patients with liver metastasis. We sought to characterize the efficacy of specific fulvestrant-based combination treat...

Approximately 70% of human breast cancers express estrogen receptor-α (ERα), providing a potential target for endocrine therapy. However, 30%-40% of patients with ER+ breast cancer still experiences recurrence and metastasis, with a 5-year relative overall survival rate of 24%. In this study, we identified NAMPT, an important enzyme in nicotinamide...

Background: Hormone receptor-positive (HR+) metastatic breast cancer (MBC) contributes to nearly 70% of breast cancer-related deaths. The liver is the third most common site for metastasis in breast cancer, and liver involvement has been found to have a poor prognosis. One contributing factor is resistance to hormonal treatments. Furthermore, estro...

Background: African American (AA) women are less likely to develop breast cancer but when they do, their mortality rates are 40% higher compared to Non-Hispanic White (NHW) women. This disparity is particularly striking among ER+ breast cancer cases. The purpose of this study is to examine whether there are racial differences in metabolic and molec...

Approximately 70% of human breast cancers express estrogen receptor alpha (ERα), providing a potential for targeted endocrine therapy for patients. Unfortunately, 30-40% of ER+ patients still experience recurrence and metastasis, with a 5-year relative overall survival rate of just 24% for patients with metastatic disease. Previously, we described...

Background Estrogen receptor-positive (ER+) metastatic breast cancer (MBC) contributes to nearly 70% of breast cancer-related deaths. Liver metastasis is the third most common site and has been found to carry a poor prognosis. One contributing factor is resistance to available treatments. Meanwhile, estrogen receptor alpha gene (ESR1) activating mu...

Development of targeted therapies will be a critical step towards reducing the mortality associated with triple-negative breast cancer (TNBC). To achieve this, we searched for targets that met three criteria: (1) pharmacologically targetable, (2) expressed in TNBC, and (3) expression is prognostic in TNBC patients. Since nuclear receptors have a we...

Wnt ligand WNT4 is critical in female reproductive tissue development, with WNT4 dysregulation linked to related pathologies including breast cancer (invasive lobular carcinoma, ILC) and gynecologic cancers. WNT4 signaling in these contexts is distinct from canonical Wnt signaling yet inadequately understood. We previously identified atypical intra...

Approximately 70% of human breast cancers express estrogen receptor alpha (ERα), providing a potential for targeted endocrine therapy for patients. Unfortunately, 30-40% of ER+ patients still experience recurrence and metastasis, with a 5-year relative overall survival rate of just 24% for patients with metastatic disease. Previously, we described...

Simple Summary Poly- and perfluoroalkylated substances (PFAS) are industrial chemicals found in many household products that persist in the environment. While several excellent review articles exist on the potential harmful effects of PFAS, there are few focused on cancer. This concise and streamlined mini-review focuses on summarizing molecular me...

The median overall survival of patients with metastatic breast cancer is only 2-3 years, and for patients with untreated liver metastasis, it is as short as 4-8 months. Improving the survival of women with breast cancer requires more effective anti-cancer strategies, especially for metastatic disease. Nutrients can influence tumor microenvironments...

Endocrine-disrupting chemicals (EDCs) are known contributors to breast cancer development. EDC exposures commonly occur through food packaging, cookware, fabrics, and personal care products as well as through the environment. Increasing evidence highlights disparities in EDC exposure across racial/ethnic groups, yet breast cancer research continues...

Estrogen receptor-positive (ER+) metastatic tumors contribute to nearly 70% of breast cancer-related deaths. Most patients with ER+ metastatic breast cancer (MBC) undergo treatment with the estrogen receptor antagonist fulvestrant as standard of care. Yet, among such patients, metastasis in liver is associated with reduced overall survival compared...

Per- and polyfluorinated alkyl substances (PFAS) are a large family of widely used synthetic chemicals that are environmentally and biologically persistent and present in most individuals. Chronic PFAS exposure have been linked to increased prostate cancer risk in occupational settings, however, underlying mechanisms have not been interrogated. Her...

Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals utilized in various industrial settings and include products such as flame retardants, artificial film-forming foams, cosmetics, and non-stick cookware, among others. Epidemiological studies suggest a link between increased blood PFAS levels and prostate cancer incidence, but the me...

About 20–30% of premenopausal women have metabolic syndrome, and the number is almost double in postmenopausal women, and these women have an increased risk of hepatosteatosis. Postmenopausal women with metabolic syndrome are often treated with hormone replacement therapy (HRT), but estrogens in currently available HRTs increase the risk of breast...

Estrogen receptor-positive (ER ⁺ ) metastatic tumors contribute to nearly 70% of breast cancer-related deaths. Most patients with ER ⁺ metastatic breast cancer (MBC) undergo treatment with the estrogen receptor antagonist fulvestrant (Fulv) as standard-of-care. Yet, among such patients, metastasis in liver is associated with reduced overall surviva...

Introduction: Approximately 70% of human breast cancers express estrogen receptor alpha (ERα), providing the potential for targeted endocrine therapy for patients. Unfortunately, 30-40% of ER+ patients still experience recurrence and metastasis with a 5-year relative overall survival rate of just 24%. Previously, we described metabolic changes in m...

Coronary microvascular disease (CMD) is a common form of heart disease in postmenopausal women. It is not due to plaque formation but dysfunction of microvessels that feed the heart muscle. The majority of the patients do not receive a proper diagnosis, are discharged prematurely and must go back to the hospital with persistent symptoms. Because of...

Cholesterol has been implicated in the clinical progression of breast cancer, a disease that continues to be the most commonly diagnosed cancer in women. Previous work has identified the cholesterol metabolite, 27-hydroxycholesterol (27HC), as a major mediator of the effects of cholesterol on breast tumor growth and progression. 27HC can act as an...

Introduction: Coronary microvascular disease (CMD) affects small arteries that feed the heart and is more prevalent in postmenopausal women. Since CMD and Coronary artery disease (CAD) have distinct pathologies, but are treated the same way, the majority of the patients with CMD do not receive a proper diagnosis and treatment, which in turn results...

Nuclear receptors are critically important in normal and disease physiology. Recent advances have created opportunities to expand our success in nuclear receptor (NR) basic and translational research, but this field lacks a platform to lay the collaborative groundwork for aspiring and upcoming leaders in the field. Nuclear Receptor IMPACT (Interdis...

Previously, quality of life (Qol) has been defined as an individual’s evaluation of a satisfactory life as a whole (i.e. physically, mentally, psychologically, and socially). Only a few studies have examined the racial differences between QoL and risk factors associated with health, demographics, and lifestyle in midlife women. Thus, the purpose of...

Abstract Screening agrochemicals and pharmaceuticals for potential liver toxicity is required for regulatory approval and is an expensive and time-consuming process. The identification and utilization of early exposure gene signatures and robust predictive models in regulatory toxicity testing has the potential to reduce time and costs substantiall...

The majority of breast cancer specific deaths in women with estrogen receptor positive (ER+) tumors occur due to metastases that are resistant to therapy. There is a critical need for novel therapeutic approaches to achieve tumor regression and/or maintain therapy responsiveness in metastatic ER+ tumors. The objective of this study was to elucidate...

Diet and lifestyle choices contribute to obesity and liver disease. Broccoli, a brassica vegetable, may mitigate negative effects of both diet and lifestyle. Currently, there are no clinically relevant, established molecular biomarkers that reflect variability in human absorption of brassica bioactives, which may be the cause of variability/inconsi...

Introduction Racial disparities in breast cancer (BrCa) mortality are well documented. We previously reported that African American (AA) women with estrogen receptor-positive (ER+) BrCa have a 4-fold higher rate of death compared to non-Hispanic whites (white) after controlling for stage at diagnosis and treatment initiation. This suggests that rac...

Introduction: Approximately 70% of human breast cancers express estrogen receptor alpha (ERα), providing a potential for targeted endocrine therapy for patients. Unfortunately, 30-40% of ER+ patients still experience recurrence and metastasis with a 5-year relative overall survival rate of just 24%. The tumor microenvironment (TME) plays a key role...

Background Quality of Life (QoL) is a major indicator of an individual’s overall health. Only a few studies have examined the racial differences between QoL, and risk factors associated with health, demographics, and lifestyle in midlife women. Thus, the purpose of our study is to determine racial differences in QoL in menopausal women due to lifes...

Previously, quality of life (Qol) has been defined as an individual’s evaluation of a satisfactory life as a whole (i.e. physically, mentally, psychologically, and socially). Only a few studies have examined the racial differences between QoL, and risk factors associated with health, demographics, and lifestyle in midlife women. Thus, the purpose o...

Previously, quality of life (Qol) has been defined as an individual’s evaluation of a satisfactory life as a whole (i.e. physically, mentally, psychologically, and socially). Only a few studies have examined the racial differences between QoL, and risk factors associated with health, demographics, and lifestyle in midlife women. Thus, the purpose o...

Hepatocellular carcinoma (HCC) is the most common liver cancer with a higher incidence in males. Here, we report that the spontaneous HCC development subsequent to the deletion of both Farnesoid X Receptor and Small Heterodimer Partner (DKO) mimics the sex-specific incidence seen clinically. In female DKO mice, we find lower levels of circulating b...

Breast cancer (BC) mortality for African-American (AA) women in the U.S. is 40% higher than that for non-Hispanic white (Caucasian) women, even though these racial groups have the same incidence rate. The racial disparities might be attributed to socioeconomic status differences; however, they might as well be due to genetic and other nongenetic fa...

p>Although there have been nationwide reductions in cancer death recently, liver cancer mortality remains a problem in rural Illinois. Research scientists anticipate that exposure to environmental toxicants in rural Illinois may be possible causes of increased liver cancer mortality in females. The purpose of our study is to identify potential biom...

African American (AA) women have a 4- to 5-fold greater risk of death from hormone receptor-positive (HR +) breast cancer (BC) compared to white women, even after controlling for stage at diagnosis, treatment, and other prognostic factors. Biologic mechanisms are activated in HR + BC arising in AA women that result in a higher rate of distant metas...

The transcription factor FOXM1 is up-regulated and overexpressed in aggressive, therapy-resistant forms of hormone receptor-positive and triple negative breast cancers, and is associated with less good patient survival. FOXM1 signaling is also a key driver in many other cancers. Here, we identify a new class of compounds effective in suppressing FO...

Breast cancer is the second leading cause of cancer mortality among women. Mammography and tumor biopsy followed by histopathological analysis are the current methods to diagnose breast cancer. Mammography does not detect all breast tumor subtypes, especially those that arise in younger women or women with dense breast tissue, and are more aggressi...

The transcription factor FOXM1 is upregulated and overexpressed in aggressive, therapy-resistant forms of hormone receptor-positive and triple negative breast cancers, and is associated with less good patient survival. FOXM1 signaling is also a key driver in many other cancers. Here, we identify a new class of compounds effective in suppressing FOX...

Chest pain with non-obstructive coronary artery disease (NOCAD) occurs more frequently in women than in men and is mainly related to coronary microvascular disease (CMD). The majority of CMD patients are postmenopausal women, suggesting a role for lack of estrogens in the development and progression of CMD. Patients are often discharged without a c...

Although there have been nationwide reductions in recent cancer death, liver cancer mortality remains to be a problem in rural Illinois. Researchers anticipate that exposure to environmental toxicants in rural Illinois, may be possible causes of increased liver cancer mortality in females. The purpose of our study is to identify potential biomarker...

BACKGROUND: African American (AA) women have a 4-5 fold greater risk of death from estrogen and/or progesterone receptor positive (ER/PR positive) breast cancer compared to non-Latina white (white) women, even after controlling for stage at diagnosis, treatment, and other prognostic factors. The purpose of this study is to examine whether there are...

Majority of breast cancer specific deaths in women with ERα (+) tumor occur due to metastases that are resistant to endocrine therapy. There is a critical need for novel therapeutic approaches to prevent or delay recurrence of ERα (+) tumors. The objective of this study was to elucidate the role of mitochondrial pathways that are activated in the p...

Although there have been nationwide reductions in recent cancer death, liver cancer mortality remains to be a problem in rural Illinois. Researchers anticipate that exposure to environmental toxicants in rural Illinois, may be possible causes of increased liver cancer mortality in females. The purpose of our study is to identify potential biomarker...

Objectives: The diet in combination with lifestyle are contributing factors to obesity-associated diseases including type II diabetes, non-alcoholic hepatic diseases, cardiovascular disease and cancer. Broccoli, a brassica vegetable, can reduce the negative effects of a detrimental diet and sedentary lifestyle that can lead to obesity and impede t...

Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver diseases in the United States. Simple and benign steatosis can gradually develop into the more serious conditions of nonalcoholic steatohepatitis (NASH) and cirrhosis. Population studies have demonstrated that men and postmenopausal women have higher incidences of NA...

A majority of breast cancer specific deaths in women with ERα (+) tumors occur due to metastases that are resistant to endocrine therapy. There is a critical need for novel therapeutic approaches to resensitize recurrent ERα (+) tumors to endocrine therapies. The objective of this study was to elucidate mechanisms of improved effectiveness of combi...

Obesity is a risk factor for postmenopausal estrogen receptor alpha (ERα)-positive (ER+) breast cancer. Molecular mechanisms underlying factors from plasma that contribute to this risk and how these mechanisms affect ERα signaling have yet to be elucidated. To identify such mechanisms, we performed whole metabolite and protein profiling in plasma s...

Estrogens and estrogen receptors (ERs) regulate metabolism in both normal physiology and in disease. The metabolic characteristics of intrinsic breast cancer subtypes change based on their ER expression. Crosstalk between estrogen signaling elements and several key metabolic regulators alters metabolism in breast cancer cells, and enables tumors to...

Majority of breast cancer specific deaths occur in women with recurrent, ERα (+), metastatic tumors that are endocrine therapy resistant. There is a critical need for novel therapeutic approaches to resensitize recurrent ERα (+) tumors to endocrine therapies. The objective of this study was to elucidate mechanisms of improved effectiveness of combi...

For the past four decades, dietary fat intake has composed a significant portion of the typical Western diet, at 33-35% of total kilocalories. Approximately 8% of this dietary fat is from consumption of deep fat fried foods. Oil has been demonstrated to be absorbed by food during frying and contributes between 8 to 40% of the food’s final weight. A...

Residential characteristics in urban neighborhoods impacts health and might be an important factor contributing to health disparities, especially in the African American population. The purpose of this systematic review is to understand the relationship between urban neighborhood and residential factors and breast cancer incidence and prognosis in...

Certain residential characteristics in urban neighborhoods have shown to have negative impacts on health, especially in the African American population. The purpose of this systematic review is to understand the relationship between urban neighborhood and residential factors and breast cancer risk, incidence, stage at diagnosis/late stage diagnosis...

Conjugated estrogens (CE) and Bazedoxifene (BZA) combination is used to alleviate menopause-associated symptoms in women. CE+BZA undergo first-pass-metabolism in the liver and deconjugation by gut microbiome via β-glucuronidase (GUS) enzyme inside the distal gut. To date, the impact of long-term exposure to CE+BZA on the gut microbiome or GUS activ...

Residential characteristics in urban neighborhoods impact health and might be important factors contributing to health disparities, especially in the African American population. The purpose of this systematic review is to understand the relationship between urban neighborhood and residential factors and breast cancer incidence and prognosis in Afr...

The bazedoxifene and conjugated estrogens (CE+BZA) combination has been shown to prevent visceral adiposity and weight gain after ovariectomy. However, its impact on the liver transcriptomes associated with prevention of hepatosteatosis is yet to be determined. In the present study, we use liver transcriptomics and plasma metabolomics analysis to c...

Cytoscape networks of GO terms associated with CE+BZA up- or down-regulated genes. (A) Downregulated and (B) upregulated GO terms are shown in blue or red, respectively. (EPS)

Relative abundance of metabolites from plasma of mice treated with various estrogens for six weeks. (XLSX)

Composition of conjugated estrogens (CE). (EPS)

Due to declining estrogen levels during menopause, NAFLD prevalence is higher in postmenopausal women compared to in premenopausal women or in men. Postmenopausal women are more susceptible to weight gain, fat redistribution and dyslipidemia, all major hallmarks of metabolic syndrome associated with increased NAFLD risk. Gut microbiota plays import...