We are a research group interested in studying the underlying mechanisms of how mechanobiology plays a role in cancer progression. Particularly, we are interested in biochemical and mechanical cues from tumor microenvironment that alter mechanical properties of cancer and stromal cells and ultimately change cancer cell behavior including migration and drug responses. By identifying molecular mediators that promote cancer cell survival and motility, we aim to develop novel anti-cancer treatment strategies.
Postdoctoral Research Fellow in Cancer Research in the Kim Laboratory
Metastasis is a multistep process and the mechanical properties or mechanotype of single cells play a critical role in each step of metastasis. Cellular mechanotype, which contributes to cellular functions including cell migration, can be regulated by mechanical and soluble extracellular cues. However, which soluble factors, and combination of environmental cues, regulate cellular mechanotype is poorly understood. A critical challenge in the field of mechanobiology is to identify soluble factors and to understand how soluble cues are translated into cell mechanotype; this would enable key molecular mediators and pathways to be exploited therapeutically as the molecules that regulate mechanotype also regulate cell contractility and invasion. Hyperglycemia is associated with obesity, and is a well-known risk factor for breast cancer including TNBC. The overall objective of this project is to examine the effects of glucose on cellular mechanotype changes and to develop compelling approaches to TNBC therapy by targeting glucose-mediated pathways that regulate mechanotype. The overarching hypothesis is that hyperglycemia in obesity regulates cancer cell mechanotype and enhances metastasis, and that understanding these pathways will lead to new therapies for TNBC in obese patients.
Treatment for metastatic triple-negative breast cancer (mTNBC) is limited due to lack of targeted therapy. Recently, an immunotherapy using atezolizumab was approved for the treatment of programmed cell death ligand 1 (PD-L1)-positive mTNBC. However, clinical trials show mixed results and patient response rates vary. For example, despite the success of Impassion130 study, the NeoTRIPaPDL1 trial showed there is no therapeutic benefit of atezolizumab (NCT002620280). Mechanisms of how tumor cells evade cytotoxicity by immune cells are still poorly understood. Cancer cells are known to evade immune surveillance by expressing PD-L1. Also, failure to recruit T cells into tumors, called innate evasion, results in cancer immune evasion. Despite the critical role of the physical and mechanical aspects in immune response at the cellular level, the role of the mechanical properties of cancer cells and immune cells in tumor immune evasion are still poorly understood. Cellular mechanotype is a key factor in regulating immune response: immune cell deformability is critical for immune synapse formation and the infiltration of T cells into the tumor requires them to deform through tight spaces. Moreover, a recent study showed that cancer cells modulate their immune response by the remodeling of their actin cytoskeleton, which is a primary regulator of cellular mechanotype. If we could understand molecular mechanisms of how tumor and immune cell mechanotype regulate cancer immunity, this would enable us to develop more effective immunotherapies. Here we will test the hypothesis that modulating cancer and immune cell mechanotypes through actin remodeling or cellular force generation will tune the activation of an antitumor immune response against breast cancer cells.
We aim to identify key pathways/components that are shared by autophagy and mechanotype regulation in breast cancer cells with hyperglycemic condition. Metabolic syndrome accompanies hyperglycemia which regulates metabolic pathways including induction of reactive oxygen species (ROS), and such redox imbalance promotes autophagy. Autophagy has been implicated in cancer progression including metastasis and recent preclinical and clinical findings provide evidence that inhibition of autophagy has promising anticancer effects. While the role of metabolic stress-induced autophagy in cancer metastasis has been demonstrated in various cancer types at nearly every step of the metastatic cascade, the molecular mechanisms of how autophagy impacts metastasis is incompletely understood. In breast cancer, some studies suggest an association between increased autophagy and metastasis. In contrast, other recent studies show induction of autophagy suppresses metastasis. If we could better understand detailed mechanisms of how hyperglycemia-induced autophagy governs the emergence of metastasis, more effective therapeutic treatment plan can be developed to suppress metastasis and/or eliminate circulating tumor cells. We will test the hypothesis that hyperglycemia induced-autophagy promotes breast cancer metastasis through modulating mechanotype of cancer cells.
Tae-Hyung Kim, Ph.D.
B.S. Sungkyunkwan University (2002), South Korea
M.S. Seoul National University (2005), South Korea
Ph.D. North Carolina State University (2011), Raleigh, NC
Postdoc University of North Carolina at Chapel Hill (2012-2014), Chapel Hill, NC
Postdoc University of California at Los Angeles (2014-2020), Los Angeles, CA
We are actively searching for talented and highly motivated postdocs and graduate students as well as undergraduate researchers to study mechanobiology in cancer research. If you are interested in any position, please send your CV and research statement to Tae-Hyung.
Email: takim@salud.unm.edu
Metastasis is a multistep process and the mechanical properties or mechanotype of single cells play a critical role in each step of metastasis. Cellular mechanotype, which contributes to cellular functions including cell migration, can be regulated by mechanical and soluble extracellular cues. However, which soluble factors, and combination of environmental cues, regulate cellular mechanotype is poorly understood. A critical challenge in the field of mechanobiology is to identify soluble factors and to understand how soluble cues are translated into cell mechanotype; this would enable key molecular mediators and pathways to be exploited therapeutically as the molecules that regulate mechanotype also regulate cell contractility and invasion. Hyperglycemia is associated with obesity, and is a well-known risk factor for breast cancer including TNBC. The overall objective of this project is to examine the effects of glucose on cellular mechanotype changes and to develop compelling approaches to TNBC therapy by targeting glucose-mediated pathways that regulate mechanotype. The overarching hypothesis is that hyperglycemia in obesity regulates cancer cell mechanotype and enhances metastasis, and that understanding these pathways will lead to new therapies for TNBC in obese patients.
Treatment for metastatic triple-negative breast cancer (mTNBC) is limited due to lack of targeted therapy. Recently, an immunotherapy using atezolizumab was approved for the treatment of programmed cell death ligand 1 (PD-L1)-positive mTNBC. However, clinical trials show mixed results and patient response rates vary. For example, despite the success of Impassion130 study, the NeoTRIPaPDL1 trial showed there is no therapeutic benefit of atezolizumab (NCT002620280). Mechanisms of how tumor cells evade cytotoxicity by immune cells are still poorly understood. Cancer cells are known to evade immune surveillance by expressing PD-L1. Also, failure to recruit T cells into tumors, called innate evasion, results in cancer immune evasion. Despite the critical role of the physical and mechanical aspects in immune response at the cellular level, the role of the mechanical properties of cancer cells and immune cells in tumor immune evasion are still poorly understood. Cellular mechanotype is a key factor in regulating immune response: immune cell deformability is critical for immune synapse formation and the infiltration of T cells into the tumor requires them to deform through tight spaces. Moreover, a recent study showed that cancer cells modulate their immune response by the remodeling of their actin cytoskeleton, which is a primary regulator of cellular mechanotype. If we could understand molecular mechanisms of how tumor and immune cell mechanotype regulate cancer immunity, this would enable us to develop more effective immunotherapies. Here we will test the hypothesis that modulating cancer and immune cell mechanotypes through actin remodeling or cellular force generation will tune the activation of an antitumor immune response against breast cancer cells.
We aim to identify key pathways/components that are shared by autophagy and mechanotype regulation in breast cancer cells with hyperglycemic condition. Metabolic syndrome accompanies hyperglycemia which regulates metabolic pathways including induction of reactive oxygen species (ROS), and such redox imbalance promotes autophagy. Autophagy has been implicated in cancer progression including metastasis and recent preclinical and clinical findings provide evidence that inhibition of autophagy has promising anticancer effects. While the role of metabolic stress-induced autophagy in cancer metastasis has been demonstrated in various cancer types at nearly every step of the metastatic cascade, the molecular mechanisms of how autophagy impacts metastasis is incompletely understood. In breast cancer, some studies suggest an association between increased autophagy and metastasis. In contrast, other recent studies show induction of autophagy suppresses metastasis. If we could better understand detailed mechanisms of how hyperglycemia-induced autophagy governs the emergence of metastasis, more effective therapeutic treatment plan can be developed to suppress metastasis and/or eliminate circulating tumor cells. We will test the hypothesis that hyperglycemia induced-autophagy promotes breast cancer metastasis through modulating mechanotype of cancer cells.
Tae-Hyung Kim, Ph.D.
B.S. Sungkyunkwan University (2002), South Korea
M.S. Seoul National University (2005), South Korea
Ph.D. North Carolina State University (2011), Raleigh, NC
Postdoc University of North Carolina at Chapel Hill (2012-2014), Chapel Hill, NC
Postdoc University of California at Los Angeles (2014-2020), Los Angeles, CA
We are actively searching for talented and highly motivated postdocs and graduate students as well as undergraduate researchers to study mechanobiology in cancer research. If you are interested in any position, please send your CV and research statement to Tae-Hyung.
Email: takim@salud.unm.edu
Tae-Hyung Kim. Ph.D.
Department of Pathology
Cancer Research Facility, Room 209
University of New Mexico School of Medicine
Albuquerque, New Mexico 87131
Email: takim@salud.unm.edu
Phone: (505) 272-9748 (office)
Phone: (505) 272-9439 (lab)
Personal Website: http://thekimlab.net
Shipping Address:
University of New Mexico
915 Camino de Salud. NE
ATTN: CRF 209
Albuquerque, NM 87131
