Research Projects

Project 1

The word ‘Oncofertility’ combines Oncology and Fertility and was coined in 2006 by Dr. Teresa K. Woodruff at Northwestern University. The goal of Oncofertility is to provide and expand the possible options for the reproductive future of young cancer patients. When young cancer patients including children, teens, and young adults receive the devastating news that they have cancer, they face fear in many ways. They are fighting against a brutal disease that changes their childhood playtime with friends, college plans, early careers, etc. Life-saving treatments such as cancer therapy unintentionally affect non-cancerous cells in their bodies. One of the most serious side effects is the loss of eggs (oocytes) and sperm, threatening their future fertility. In addition to fertility concerns, loss of endocrine support in females can cause a cascade of medical and quality-of-life problems beginning in young cancer patients. Damage to reproductive organs like the ovary can lead to genetically damaged oocytes, early menopause, and primary ovarian insufficiency. The symptoms of premature ovarian insufficiency include sterility, osteoporosis, depression, anxiety, cardiovascular disease, and dementia and generally compromise the quality of life for young cancer patients. However, the current management options for primary ovarian insufficiency are inadequate. Successful Oncofertility requires meaningful communication and prompt decision among patients, family, reproductive endocrinologists, oncologists, patient navigators, and other health care providers. Patients and families should be provided with enough information regarding the drugs that pose a threat to fertility and all possible options for disruptions to fertility.  Currently, procedures for the preservation of oocytes, embryos, and ovarian tissues are available options for young adults. However, those options are not available for young prepubertal cancer patients. Young girls receiving cancer therapies are faced with delayed menarche, the possible necessity of hormone replacement therapy for their lifetime, and the mental and emotional stress of not being able to have children. Thus, developing an effective intervention to prevent the loss of ovarian function is an unmet need in the field. In the Kim Laboratory, we focus on understanding the mechanisms by which specific chemotherapeutic agents deplete oocytes. We are currently investigating ways to lessen the effects of any disease or treatment on ovarian function and develop physician-guided tools that will facilitate communication and translation between basic research and clinical practice.

Project 2

Cachexia has been described as ‘the last illness’ that humans can face (Lok 2015). It is a word from the Greek, kakos and hexis, meaning bad condition. The main characteristics of cachexia are represented by loss of skeletal muscle and body fat, causing asthenia, anorexia, anemia, and fatigue. The patients’ symptoms are complicated and their malnutrition condition cannot be reversed simply by increasing nutrition uptake although some appetite stimulants or specific diets, like the ketogenic diet, may help in certain patients. It occurs in patients suffering from chronic infection, kidney disease, heart failure, and cancer. Approximately 50% of all cancer patients have cachexia symptoms, 80% of patients with advanced cancers develop cachexia, and 20% of cancer patients die of cachexia. Cancer patients with pancreatic cancer, non-small lung cancer,  colorectal cancer, gastric cancer, melanoma, or thoracic and head and neck malignancies are prone to develop cachectic symptoms. Although the cancers above may occur from different origins, their cachectic symptoms at the last stage of the disease are similar among cancer patients, suggesting that the causal factors and the mechanisms behind those induce cachectic symptoms are related. Several factors have been proposed to induce cachectic symptoms in human patients: interleukin 6, myostatin, parathyroid hormone/parathyroid hormone-related protein, C-reactive protein, and tumor necrosis factor-alpha. Thus, common metabolic pathways disrupted by these key mediators have been proposed as ideal targets for reducing symptoms. Despite a body of evidence demonstrating overexpression of various factors in cachexia, there have been no studies on the regulation of the expression of those cachectic factors, especially activin A. Thus, we study the mechanisms regulating the overproduction of activin A and the transcriptional and metabolic reprogramming of adipose tissue by activin A. This study will answer the question of how specific cancer cells acquire changes in the overproduction of activin A that ultimately result in uncontrolled growth and the cachectic condition and how adipose tissues respond to activin A.

Reference: Lok, C. (2015) Nature Dec. 10;528(7581):182-3