This document outlines the scientific process of planning and conducting research through asking questions, developing hypotheses, constructing models, testing models, and improving models based on results. It provides historical examples of this process, including Mendel's experiments on genetic traits in pea plants, studies on tumor heterogeneity and drug resistance in cancer, and identification of factors that induce pluripotency in somatic cells. The document emphasizes defining the research question and scope, hypothesizing driving factors, constructing testable models, evaluating output to identify gaps, and using feedback to iteratively improve models.
1. Aging and limited lifespan are caused by the cost of complexity maintenance. Lifespan is determined by the functional stem cell output to tissue damage. Cancer arises when the size functional stem cell pool is small, which may take place in the early life stage or during aging stem cell decline. Changing life history can modify stem cell aging and cancer spectrum. Decelerating tissue damage and stem cell decline may delay cancer.
2. Immunity maintains somatic tissue integrity. Tumors may continuously form but are kept asymptomatic by immunosurveillance. Immune decline or suppression allows small tumors to outbreak and become symptomatic, promoting cancer. Allocating resources away from immunity through lifestyle causes immune suppression.
3. Evolutionary and life history
Bad Luck vs Peto's Paradox in Caner incidencesChi-Ping Day
1. Cancer risk varies among tissues and can be partially explained by the number of stem cell divisions, with more divisions correlating to higher risk. However, external risk factors also contribute significantly.
2. While the number of stem cell divisions correlates with lifetime cancer risk, this does not distinguish the influence of intrinsic versus extrinsic factors. Other evidence suggests extrinsic factors account for over 70% of risk for most common cancers.
3. Peto's paradox, the observation that cancer risk does not scale linearly with body size, may be explained by the independent effects of stem cell division rates and numbers varying among tissues, though natural selection has also influenced lower risks in some highly proliferative tissues.
Emerging Clinical Applications of CRISPR-Cas9 as Promising Strategies in Gene...Chi-Ping Day
CRISPR/Cas9 gene editing shows promise for correcting diseases through gene therapy and targeted changes. Current applications include editing T-cells to produce CAR T-cells for cancer therapy and editing retinal cells in rats to treat retinitis pigmentosa. Additional areas of focus include eliminating HIV from cells, correcting the Fah mutation in mice, and overcoming issues like delivery efficiency and off-target effects. Looking ahead, cell therapies and local treatments for eye/ear diseases appear promising applications for CRISPR's precise gene editing capabilities.
Facilitating Advanced Drug Development and Evaluation Using CRISPR-Cas9 Techn...Chi-Ping Day
This document discusses using CRISPR/Cas9 technology to facilitate advanced drug development. It describes drug development as a process of disease modeling that involves: 1) Identifying the dysfunctional system that causes the disease, 2) Generating hypotheses for target identification, 3) Validating targets by testing hypotheses, 4) Evaluating outcomes, and 5) Reconfiguring the system. CRISPR/Cas9 offers advantages like reducing confounding effects through specific gene editing and versatile screening/validation strategies. Remaining issues include off-targets, potential DNA damage, immune response, and efficiency.
Implication of cancer biology to the futureChi-Ping Day
This document discusses how concepts from cancer biology can help predict future economic growth and transitions. It draws parallels between tumor formation and urban sprawl, noting how both systems evolve from an initial niche to expand peripherally as the environment deteriorates. It also summarizes a model showing how organizational growth is driven by depletion of non-renewable resources. The document argues that societies must transition to new energy sources to avoid economic crises, and suggests high-population urban centers are well-positioned to transition to renewable and low-power energy systems through virtualization, recycling, and localized manufacturing enabled by information and computing technologies.
This document outlines the scientific process of planning and conducting research through asking questions, developing hypotheses, constructing models, testing models, and improving models based on results. It provides historical examples of this process, including Mendel's experiments on genetic traits in pea plants, studies on tumor heterogeneity and drug resistance in cancer, and identification of factors that induce pluripotency in somatic cells. The document emphasizes defining the research question and scope, hypothesizing driving factors, constructing testable models, evaluating output to identify gaps, and using feedback to iteratively improve models.
1. Aging and limited lifespan are caused by the cost of complexity maintenance. Lifespan is determined by the functional stem cell output to tissue damage. Cancer arises when the size functional stem cell pool is small, which may take place in the early life stage or during aging stem cell decline. Changing life history can modify stem cell aging and cancer spectrum. Decelerating tissue damage and stem cell decline may delay cancer.
2. Immunity maintains somatic tissue integrity. Tumors may continuously form but are kept asymptomatic by immunosurveillance. Immune decline or suppression allows small tumors to outbreak and become symptomatic, promoting cancer. Allocating resources away from immunity through lifestyle causes immune suppression.
3. Evolutionary and life history
Bad Luck vs Peto's Paradox in Caner incidencesChi-Ping Day
1. Cancer risk varies among tissues and can be partially explained by the number of stem cell divisions, with more divisions correlating to higher risk. However, external risk factors also contribute significantly.
2. While the number of stem cell divisions correlates with lifetime cancer risk, this does not distinguish the influence of intrinsic versus extrinsic factors. Other evidence suggests extrinsic factors account for over 70% of risk for most common cancers.
3. Peto's paradox, the observation that cancer risk does not scale linearly with body size, may be explained by the independent effects of stem cell division rates and numbers varying among tissues, though natural selection has also influenced lower risks in some highly proliferative tissues.
Emerging Clinical Applications of CRISPR-Cas9 as Promising Strategies in Gene...Chi-Ping Day
CRISPR/Cas9 gene editing shows promise for correcting diseases through gene therapy and targeted changes. Current applications include editing T-cells to produce CAR T-cells for cancer therapy and editing retinal cells in rats to treat retinitis pigmentosa. Additional areas of focus include eliminating HIV from cells, correcting the Fah mutation in mice, and overcoming issues like delivery efficiency and off-target effects. Looking ahead, cell therapies and local treatments for eye/ear diseases appear promising applications for CRISPR's precise gene editing capabilities.
Facilitating Advanced Drug Development and Evaluation Using CRISPR-Cas9 Techn...Chi-Ping Day
This document discusses using CRISPR/Cas9 technology to facilitate advanced drug development. It describes drug development as a process of disease modeling that involves: 1) Identifying the dysfunctional system that causes the disease, 2) Generating hypotheses for target identification, 3) Validating targets by testing hypotheses, 4) Evaluating outcomes, and 5) Reconfiguring the system. CRISPR/Cas9 offers advantages like reducing confounding effects through specific gene editing and versatile screening/validation strategies. Remaining issues include off-targets, potential DNA damage, immune response, and efficiency.
Implication of cancer biology to the futureChi-Ping Day
This document discusses how concepts from cancer biology can help predict future economic growth and transitions. It draws parallels between tumor formation and urban sprawl, noting how both systems evolve from an initial niche to expand peripherally as the environment deteriorates. It also summarizes a model showing how organizational growth is driven by depletion of non-renewable resources. The document argues that societies must transition to new energy sources to avoid economic crises, and suggests high-population urban centers are well-positioned to transition to renewable and low-power energy systems through virtualization, recycling, and localized manufacturing enabled by information and computing technologies.