Kristi Baker

Area of Study / Keywords

Colorectal cancer DNA repair Mucosal immunology Mismatch repair Intestinal microbiome Exosomes IgG Organoids Orthotopic tumor model Dendritic cells T cells Metastasis intestine microsatellite instability DNA damage immunity inflammation apoptosis cell stress colon intestinal epithelial cell (IEC) microbiota genotoxin homeostasis Tumor infiltrating lymphocytes (TILs) Orthotopic models

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About

Dr. Kristi Baker is currently appointed as Associate Professor in the Department of Oncology in the Faculty of Medicine & Dentistry.

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Research

Colorectal cancer occurs when epithelial cells in the intestine start to grow uncontrollably. While many events need to take place to produce , our lab is focused on studying the convergence of two very important factors. The first is the occurrence of mutations in the DNA of cells lining the intestine. These changes to the cell’s DNA lead the cell to produce altered proteins that, in turn, change the of the cell. These abnormal cells fail to respond to the normal regulatory pathways in the intestine that limit cell growth. One of the consequences of the rapid growth of cancer cells is that they do not have sufficient time to repair mistakes made as they are copying the DNA that they will transmit to their progeny. This leads to the gradual accumulation of more and more mutations over the lifetime of a and creates a situation where the genome of becomes unstable. Research has shown that this genomic instability is an important driving factor in the progression of .

The second element of cancer development that our lab studies that the immune system interacts with cancer cells. Our body’s immune system has arisen to detect abnormal proteins that are expressed by foreign invaders, such as infectious bacteria or viruses. Normally, when the immune system detects an entity that it does not recognize as "self", it is very efficient at eliminating the potential threat. Unfortunately, even though the mutations in cancer cells lead them to produce many abnormal proteins, the immune system fails to distinguish them from normal cells in the body and so it does not attack and eliminate them. How cells manage to escape from immune detection and destruction despite their abnormalities is a longstanding question in cancer research.

Our lab studies differences in how the specialized mucosal immune in the intestine sees with different patterns of genomic instability and how this translates into different forms of anti-tumor immune responses.

We are currently focused on answering questions in three major areas:

1. What kinds of immune responses are associated with disruptions to different DNA repair pathways that produce different patterns of genomic instability?
2. Are different kinds of microbial species living in the intestine (aka "the microbiota") associated with cancers having different underlying patterns of genomic instability? How do microbial metabolites and genotoxic substances alter a ’s immunogenicity?
3. How does DNA damage resulting from chemotherapy and radiotherapy influence anti-tumor immunity? Is this related to the poor response rates of colorectal cancer patients new forms of adjuvant immunotherapy?

We expect that our work will give the cancer community a better understanding of how develop in the context of a complex microenvironment containing immune cells and microbial agents and that our research will help to identify new ways to stimulate the body’s natural system to kill cancer cells.

   

ONCOL 253 - Cancer Biology

An introduction to the biology of cancer highlighting features that distinguish normal cells from cancer cells. Specific topics include the genetic basis of cancer, control of cell proliferation, invasion and metastasis, mechanism of action of cancer drugs and the development of resistance.

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Browse more courses taught by Kristi Baker

Mosley S.R., Baker K.

STAR Protocols. 2022 March; 3 (1) 10.1016/j.xpro.2022.101165

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Mowat C., Mosley S.R., Namdar A., Schiller D., Baker K.

JOURNAL OF EXPERIMENTAL MEDICINE. 2021 July; 218 (9) 10.1084/jem.20210108

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Hubbard J.J., Pyzik M., Rath T., Kozicky L.K., Sand K.M.K., Gandhi A.K., Grevys A., Foss S., Menzies S.C., Glickman J.N., Fiebiger E., Roopenian D.C., Sandlie I., Andersen J.T., Sly L.M., Baker K., Blumberg R.S.

JOURNAL OF EXPERIMENTAL MEDICINE. 2020 October; 217 (10) 10.1084/JEM.20200359