Anne completed her Dr. rer. nat. at the Department of Radiotherapy and Radiation Oncology, Molecular Oncology, LMU Munich, Germany. She has a strong background in cancer biology and immunology. One of the main results of her PhD thesis is that the HSP90 inhibitor, NW457, potently radiosensitizes resistant, aggressive soft tissue sarcoma and colorectal cancer. In her postdoctoral work at Stanford University, Anne is working on determining the key drivers of metastasis in hepatocellular carcinoma with the goal to eventually target these key drivers pharmaceutically.

Dr. Li will be conducting research on abnormal DNA damage response both accelerates aging and underlies cancer pathogenesis. Because RNA translation control dictates protein expression in cells, Grace will investigate RNA translational control in response to DNA damage. The project will identify mechanisms that drive RNA translation specificity during DNA damage in cells undergoing aging process and cancer transformation.

There have been advances in the treatment of AML including the introduction of molecularly targeted therapies with the goal of minimizing toxicity and improving efficacy. The current slate of targeted therapies includes several small molecules against FLT3 signaling, aberrant histone modification and DNA methylation.  However, several have failed to produce significant improvements in clinical trials.  Recently, AXL signaling has been implicated as a prognostic indicator, mechanism of drug resistance and potential therapeutic target in AML.  The mechanism of AXL signaling in the pathogenesis of AML and drug resistance remains unclear.  The goal of my research is to see if inhibiting AXL signaling in combination with chemotherapy will result in better treatment outcomes. 

My main research interest is to exploit the tumor microenvironment to improve response to anticancer therapies. PARP inhibitors (inhibitors of DNA repair) have shown great promise preclinically, however their success has been limited in the clinic. I aim to understand the main resistance mechanisms of cancer cells and tumors to PARP inhibition, in an attempt to find the right combination therapy that will improve the efficacy of PARP inhibitors in the clinic. Despite the impressive success of cancer immunotherapies, only a fraction of patients do respond. I am interested in investigating the role of Axl in modulating the tumor immune environment with the vision to exploit the pathway for an effective immune therapy.

I joined the Giaccia lab as an undergraduate and have been working closely with Dr. Olcina on her projects. Our work focuses on whether targeting the complement system could be used to minimise treatment toxicity while improving tumour sensitivity to radiation. I have been assisting her with studying the mechanisms regulating the complement pathway in tumours, with a specific focus on the role played by components of the tumour microenvironment such as hypoxia (low oxygen regions).

Excessive accumulation of cytosolic lipid droplets defines clear cell renal cell carcinoma (ccRCC), a deadly subtype of kidney cancer with a distinctive microscopic histology and unique metabolism. Loss or mutation to the tumor suppressor gene, VHL, is the predominant genetic alteration in ccRCC and results in short circuiting of the cellular oxygen sensing machinery. The resulting constitutive activation of hypoxia inducible transcription factors (HIFs) drastically alters the metabolic behavior of the cell. Despite the universal nature of lipid accumulation in ccRCC, surprisingly little is known about the molecular events underlying the accumulation of lipid droplets during tumorigenesis. Furthermore, any contribution of lipids or lipid droplets to renal tumorigenesis has yet to be elucidated. Though the accumulation of lipids is particularly pronounced in ccRCC, many tumor types exhibit increased lipid content relative to normal tissue counterparts, and hypoxia is known to alter lipid metabolism. Our work has characterized HIF-dependent suppression of the transcriptional co-activator, PGC-1α, as a key event that drives the clear cell phenotype of ccRCC.

Breast cancer cells frequently metastasize to the skeleton, where they may either induce osteolytic bone destruction, or enter a dormant state in the marrow. In many patients, these indolent breast cancer cells eventually exit dormancy via unknown mechanisms and result in a clinically detectable bone metastasis, significantly impacting patient morbidity and mortality. We have generated data indicating that the leukemia inhibitory factor (LIF) receptor (LIFR), which is an important modulator of physiological bone remodeling, functions to maintain breast cancer cells in a dormant state in the bone marrow. Furthermore, our data suggests that extreme hypoxia, found sporadically throughout the marrow, may drive dormant tumor cells to down-regulate the LIFR and aggressively colonize the bone. The aims of my project are to 1) determine changes in gene expression as breast cancer cells transition from a dormant to invasive state in the marrow, 2) to determine the role of hypoxia in promoting tumor cell metastasis to bone and the exit from dormancy, and 3) to examine the role of LIF signaling in breast cancer bone metastasis.

Understanding how hypoxia (low oxygen) and hypoxia inducible signaling (HIF) signaling regulates cells in the bone microenvironment is critical for understanding not only the signaling mechanisms controlling normal tissue homeostasis, but also for revealing how disordered niche function contributes to tumorigenesis in the bone. The bone microenvironment displays regional areas of hypoxia, but how this contributes to tissue homeostasis is incompletely understood. We have reported that HIF signaling within the osteoblastic niche is active, controls the regulation of bone homeostasis, elevates hematopoietic stem cells in the bone marrow, and directly modulates erythropoiesis through the production of osteoblastic EPO. Furthermore, we have demonstrated that the oxygen sensing prolyl hydroxylase enzymes functionally contributes to tissue homeostasis within the bone microenvironment by acting as a molecular rheostat to regulate HIF signaling dosage, with distinctive PHD isoform combinations directing unique gene expression patterns to differentially regulate bone and blood homeostasis. Our work has expanded the knowledge of the role of hypoxia and oxygen sensing in the hematopoietic niche, supports the concept that the bone can function as an endocrine organ, and has important therapeutic implications for the treatment of pathophysiological bone and hematological disorders.

Dr. Moon analyzes the underlying mechanisms of MafF induction in cancer. In addition to her current research, Dr. Moon determines the effect of radiation in tumor DNA damage under hypoxia, which will provide crucial information in radiation biology and preclinical research.

Saravanan received his Bachelor's degree in Pharmaceutical Sciences and he is a registered pharmacist from India, and later obtained his Master’s degree in Biochemical Engineering from the Banaras Hindu University. He enjoyed and survived the harsh winter in Winnipeg, Manitoba to obtain his Doctoral degree on T-cell migration in lymph node relevant chemokine fields using microfluidic devices from the University of Manitoba, Canada. Getting interested on immune cell migration, he focused his post-doctoral research on NK cell migration relevant to tumor microenvironment at the department of Immunology, University of Manitoba for two years. Moving south to California to enjoy the warmer weather to investigate the immune cell interactions in tumor microenvironment. In his free time, he enjoys cooking with his family, enjoying Ilayaraja’s tamil melodies and watching cricket.

The standard of care for a variety of cancers consists of therapies that are associated with significant toxicity, however, relatively little is known regarding what approaches could be undertaken to reduce treatment toxicity without compromising tumor control. Strategies achieving both of these aims would increase the therapeutic window of treatments such as radiotherapy resulting in significant improvements in tumour control and overall patient quality of life. My work in the Giaccia lab aims to establish whether targeting the complement system could be used to minimise treatment toxicity while improving tumour sensitivity to radiation. To this end, I have been studying the mechanisms regulating this pathway in tumours, with a specific focus on the role played by components of the tumour microenvironment such as hypoxia (low oxygen regions). This knowledge together with an improved understanding of how radiation regulates this pathway in both tumors and normal tissues has been guiding the most effective validation of this pathway in in vivo models.

Ninety percent of cancer deaths are caused by metastasis, the process through which cancer spreads within the body. Ninna is engineering vascular networks in in vitro models of the different tissues in which metastases most frequently occur. Her goal is to develop an assay that can determine to which tissues an individual patient's cancer is most likely to metastasize. This assay will provide cancer researchers a tool for studying metastasis on a single cell level and could permit clinicians to predict the metastatic course a cancer will take in each individual patient and to identify the treatment to which that cancer will be most susceptible.

Kaushik received his Bachelor’s and Masters degree in Microbiology from University of Pune, India. After his masters, he was doing Drug Discovery Research in Lupin Research Park, India for 2 years. He did his doctoral studies at the MD Anderson Cancer Center in the Department of Epigenetics and Molecular Carcinogenesis at Houston, TX. His research was focussed on understanding the role of a oncogenic histone reader in regulation of cancer metabolism and EMT in breast cancer. In his postdoctoral work, he is interested in the identification and characterization of novel hypoxia inducible genes and study their roles in cancer. Kaushik enjoys doing photography and playing table tennis in his free time.

Kidney cancer is one of the 10 most common cancers in the United States and diagnosis rates of kidney cancer have risen in the past 20 years. Kidney cancer resists chemotherapy and other treatments almost entirely. Even when therapy proves initially successful, tumors usually develop resistance. Thus, the most effective treatment remains surgery, although this can only halt disease progression if the disease is detected early. There is therefore a drastic need for effective treatment strategies and biomarkers to enable early detection. My research focuses on the metabolic changes inherent in the development of kidney cancer. By better understanding the functional consequences and underlying mechanisms of this metabolic shift, we hope to discover new avenues by which we can more easily detect and treat this deadly disease.