Some examples of Causal Pathways in disease that KineMed Measures:

 Neurodegenerative Diseases

  • Axonal transport (cargo kinetics), incl. region specific (motor, sensory, cognitive, etc.) and neurodegenerative disease-specific (AD, PD, ALS, HD, etc.)
  • Aβ synthesis; amyloid plaque turnover (AD, Tau-opathies)
  • Huntingtin synthesis (HD)
  • Prion turnover
  • Proteome dynamics (discovery)
  • Myelin synthesis/turnover (remyelination, MS)
  • Neurotransmitter turnover (neuropsychiatry, appetite, sleep, etc.)
  • Neurogenesis
  • Microtubule turnover
  • Neuronal mitochondrial biogenesis
  • Synaptic plasticity
  • Neuroinflammation
  • Neuronal Autophagy

Cancer (biopsy, blood)

  • Tumor cell proliferation (FACS, whole tissue), neo-adjuvant design; comparison to PET proliferation; CLL kinetics
  • Circulating tumor cells (CTCs), circulating endothelial cells (CECs) - comparison to metastases in tissues and to angiogenesis in tissues.
  • Anti-tumor T-cell proliferation and activation
  • Lymphangiogenesis (metastastic spread)
  • MGUS/myeloma (urine gammopathies)
  • Myelofibrosis (BM kinetics)
  • Precancer/prevention: prostate (seminal fluid PEC vs biopsy), breast (nipple aspirate BEC vs biopsy); colon cells (fecal vs biopsy); BPH (effects of androgen/SARM Rx); DCIS; IBD
  • Activity of ribonucleotide reductase
  • DNA methylation/hypomethylation
  • Histone acetylation/de-acetylation
  • Tumor matrix turnover (hyaluronin, GAG, etc.)
  • Tumor metabolism (PPS, glycolysis, etc.)
  • Protein degradation (proteome dynamics)

Atherosclerosis, lipids:

  • RCT fluxes (genetic hypoalpha/hypoβ, rHDL Rx, niacin), macrophage/monocyte cholesterol dynamics); vs. forward fluxes (apoB particles)
  • Lipid/lipoprotein kinetics (β-particles), differences among SPARMS, de novo cholesterol synthesis
  • Vascular smooth muscle cell proliferation
  • Atheroma plaque dynamics (PET; Foxhollow biopsy method)
  • Clothing system (fibrinogen kinetics; etc.); effects of SPARMs, CETPi, etc.
  • Oxidative stress (production and clearance rates of ROS); oxidative damage (production and clearance of oxidatively modified DNA, proteins, lipids)

Inflammation, immunity, infectious diseases

  • Auto-immune Ag-specific T-cells
  • Inflammatory bowel disease colonyte turnover; psoriasis skin cell/keratin turnover
  • Cytokine production and clearance rates
  • Vaccination, (Ag-specific T-cells/NK cells and antibody; basis of long-term memory maintenance, effects of adjuvants); anti-tumor T-cell kinetics.
  • T-cell dynamics, immune activation (HIV, HCV, HepB, other chronic infections); protease-inhibitor failure; long-term non-progressors
  • Circulating virus kinetics (HepB, HIV)
  • Abcess and fluid microbial replication/prolifation (surgical, TB)
  • Lymph node T-cell recruitment

Arthritis, bone

  • Joint-space components (joint protective therapies)
  • Bone collagen kinetics (CDPs), osteopenia, drugs (e.g., glucocorticoid agonists)

Lung biology

  • Collagen synthesis (lung fibrogenesis)
  • Elastin synthesis and breakdown (emphysema)
  • Surfactant synthesis and production (toxicity)
  • Macrophage recruitment and activation          

Obesity/ diabetes

  • β-cell proliferation (PET, proteomics), β-cell mass (dilution)
  • β-cell secretory reserve (hormone synthesis/secretion)
  • Diabetic end-organ complications (advanced glycosylation product synthesis)
  • Adipose dynamics (adipogenesis, pre-adipocyte differentiation; lipolysis; adipogenesis, macrophage proliferation, de novo lipogenesis); brown fat vs. white fat metabolic fsignature
  • De novo lipogenesis (steatosis, appetite)
  • Insulin resistance/ β-cell response (pre-DM/DM)
  • Dieting fat handling (DGAT and absorption)
  • Effects of anti-psychiatric drugs (obesity, insulin resistance)
  • Differentiating PPAR gamma agonists (fluid retention, lipogenesis) 

Skin Disorders

  • Keratin/keratinocyte turnover (psoriasis, exczema)
  • Wrinkling + cosmetics (elastin, collagen, lipids, keratinocytes) 

Fibrogenesis (collagen degradation products [CDPs], biopsies)

  • Skin (scleroderma, injury)
  • Lung lavage (PIF)
  • Lymphoid tissues(HIV)
  • Kidney (urine, biopsy)
  • Liver (blood, bile, biopsy)
  • Cardiac (CDPs)
  • Wounds (surgical, traumatic, foot ulcers) 

Muscle biology (biopsy, blood, urine)

  • Mitochondrial biogenesis
  • Satellite cell proliferation
  • Protein degradation/protein synthesis (non-invasive from released proteins)
  • Muscle energetics
  • IMTG dynamics
  • Muscle mass
  • Muscle sparing statins
  • Thermogenesis Cardiac regeneration

Toxicology

  • Liver toxins (compensatory hepatocyte proliferation)
  • Oxidative stress
  • Pulmonary surfactant production 

Histokinetics (microdissection of tissue slides)

  • Cancer (grading, stratification, prognosis; efficacy in neoadjuvant setting)
  • Angiogenesis (cancer, diabetic microvascular complications)
  • Pre-cancer/dysplasia/carcinoma in situ [CIS]) - prostate (high grade prostate intraepithelial neoplasia), breast (ductal CIS), colon (polyps, CIS), bladder (CIS), cervix (high grade SIL), skin (Bowen’s disease); bronchioalveolar (CIS); etc. (“watchful waiting”, management and transition of
  • Hepatic turnover of lipid stores (steattosis), peri-portal vs. peri-venous vs. peri-cannicular metabolism and cell biology
  • Cell regeneration and healing in tissues (e.g., hepatocytes after liver injury; diabetic foot ulcers; colonocytes during treatment of IBD; myocytes after trauma or surgery)
  • Transplant assessment (kidney fibrogenesis; cardiac muscle protein synthesis and myocyte proliferation, pancreatic beta cell proliferation; immunocyte infiltration)
  • Tissue synthesis and breakdown of collagen, fibrin, actin, amyloid, other structural proteins
  • Intra-muscular triglyceride turnover (insulin sensitivity), mitochondrial biogenesis
  • Dynamics of organelles in tissues (e.g., ER stress)
  • Reticulo-endothelial cell activity (uptake, clearance)
  • Kinetic microscope (tissue dynamic mapping of macromolecules by MALDI)
  • Regional metabolic and cell biologic differences within tissues