- Sports injuries and prevention
- Lower Extremity Biomechanics and Pathologies
- Sports Performance and Training
- Shoulder Injury and Treatment
- Tendon Structure and Treatment
- Click Chemistry and Applications
- Cardiovascular Effects of Exercise
- Cardiovascular and exercise physiology
- Knee injuries and reconstruction techniques
- RNA and protein synthesis mechanisms
- Peptidase Inhibition and Analysis
- Foot and Ankle Surgery
- RNA modifications and cancer
- Ubiquitin and proteasome pathways
- Melanoma and MAPK Pathways
- Chemical Synthesis and Analysis
- Muscle metabolism and nutrition
- Diabetic Foot Ulcer Assessment and Management
- Protein Degradation and Inhibitors
- Monoclonal and Polyclonal Antibodies Research
- Exercise and Physiological Responses
- Protein Kinase Regulation and GTPase Signaling
- Hip disorders and treatments
- Injury Epidemiology and Prevention
- Computational Drug Discovery Methods
University of British Columbia
2015-2025
University of California, San Francisco
2015-2024
Canadian Sport Centre Pacific
2000-2020
Quantitative BioSciences
2018
UCSF Helen Diller Family Comprehensive Cancer Center
2017
Howard Hughes Medical Institute
1996-2016
Marine Biological Laboratory
2016
City College of San Francisco
2016
The University of Texas MD Anderson Cancer Center
2016
St. Paul's Hospital
2016
Trapoxin is a microbially derived cyclotetrapeptide that inhibits histone deacetylation in vivo and causes mammalian cells to arrest the cell cycle. A trapoxin affinity matrix was used isolate two nuclear proteins copurified with deacetylase activity. Both were identified by peptide microsequencing, complementary DNA encoding catalytic subunit (HD1) cloned from human Jurkat T library. As predicted protein very similar yeast transcriptional regulator Rpd3p, these results support role for as...
Objective: To provide an extensive and up to date database for specific running related injuries, across the sexes, as seen at a primary care sports medicine facility, assess relative risk individual injuries based on investigation of selected factors. Methods: Patient data were recorded by doctors Allan McGavin Sports Medicine Centre over two year period. They included assessment anthropometric, training, biomechanical information. A model was constructed (with odds ratios their 95%...
Activation of various cell surface receptors triggers the reorganization downstream signaling molecules into micrometer- or submicrometer-sized clusters. However, functional consequences such clustering have been unclear. We biochemically reconstituted a 12-component pathway on model membranes, beginning with T receptor (TCR) activation and ending actin assembly. When TCR phosphorylation was triggered, proteins spontaneously separated liquid-like clusters that promoted outputs both in vitro...
We analyzed cases of 320 athletes with bone scan- positive stress fractures (M = 145, F 175) seen over 3.5 years and assessed the results conservative management. The most common injured was tibia (49.1 %), followed by tarsals (25.3%), metatar sals (8.8%), femur (7.2%), fibula (6.6%), pelvis (1.6%), sesamoids (0.9%), spine (0.6%). Stress were bilateral in 16.6% cases. A significant age difference among sites found, femoral tarsal occurring oldest, fibular tibial youngest. Run ning sport at...
Background —There is no disease specific, reliable, and valid clinical measure of Achilles tendinopathy. Objective —To develop test a questionnaire based instrument that would serve as an index severity Methods —Item generation, item reduction, scaling, pretesting were used to assess the The final version consisted eight questions measured domains pain, function in daily living, sporting activity. Results range from 0 100, where 100 represents perfect score. Its validity reliability then...
AbstractIn brief: This retrospective survey of the clinical records 1,650 patients seen from 1978 to 1980 identified 1,819 injuries. Almost 60% were men, but women under age 30 had greatest risk overuse running The knee was most commonly injured site, and patellofemoral pain syndrome common injury. Most moderate severe degrees varus alignment subsequent overpronation. Because certain injuries more frequent in one sex or other, authors say future studies should differentiate by sex.
One hundred nine runners were treated conservatively without immobilization for overuse injury to the Achilles tendon. Treatment strategies directed toward re habilitation of gastrocnemius/soleus muscle-tendon unit, control inflammation and pain, biomechanical parameters. fair, 12 good, 73 excellent results reported, with a mean recovery time 5 week.Followup was incomplete in 23 cases. The three most prevalent etiological factors overtraining (82 cases), functional overpronation (61...
The active sites of 491 human protein kinase domains are highly conserved, which makes the design selective inhibitors a formidable challenge. We used structural bioinformatics approach to identify two selectivity filters, threonine and cysteine, at defined positions in site p90 ribosomal S6 (RSK). A fluoromethylketone inhibitor, designed exploit both potently selectively inactivated RSK1 RSK2 mammalian cells. Kinases with only one filter were resistant yet they became sensitized after...
We examined the spatial and temporal control of actin assembly in living Xenopus eggs. Within minutes egg activation, dynamic actin-rich comet tails appeared on a subset cytoplasmic vesicles that were enriched protein kinase C (PKC), causing to move through cytoplasm. Actin tail formation vivo was stimulated by PKC activator phorbol myristate acetate (PMA), this process could be reconstituted cell-free system. used system define characteristics distinguish associated with from other extract....
Objectives: Seventeen running training clinics were investigated to determine the number of injuries that occur in a programme designed minimise injury rate for athletes 10 km race. The relative contributions factors associated with also reported. Methods: A total 844 primarily recreational runners surveyed three trials on 4th, 8th, and 12th week 13 “In Training” clinics. Participants classified as injured if they experienced at least grade 1 injury—that is, pain only after running. Logistic...
ABSTRACT An outbreak of the novel coronavirus SARS-CoV-2, causative agent COVID-19 respiratory disease, has infected over 290,000 people since end 2019, killed 12,000, and caused worldwide social economic disruption 1,2 . There are currently no antiviral drugs with proven efficacy nor there vaccines for its prevention. Unfortunately, scientific community little knowledge molecular details SARS-CoV-2 infection. To illuminate this, we cloned, tagged expressed 26 29 viral proteins in human...
Protein kinases comprise a large family of structurally related enzymes. A major goal in kinase-inhibitor development is to selectively engage the desired kinase while avoiding myriad off-target kinases. However, quantifying inhibitor interactions with multiple endogenous live cells remains an unmet challenge. Here, we report design sulfonyl fluoride probes that covalently label broad swath intracellular kinome high efficiency. crystallography and mass spectrometry confirmed chemoselective...
Electrophilic probes that covalently modify a cysteine thiol often show enhanced pharmacological potency and selectivity. Although reversible Michael acceptors have been reported, the structural requirements for reversibility are poorly understood. Here, we report novel class of acrylonitrile-based acceptors, activated by aryl or heteroaryl electron-withdrawing groups. We demonstrate adducts these acrylonitriles undergo β-elimination at rates span more than 3 orders magnitude. These...
In eukaryotes, accurate protein synthesis relies on a family of translational GTPases that pair with specific decoding factors to decipher the mRNA code ribosomes. We present structures mammalian ribosome engaged factor⋅GTPase complexes representing intermediates translation elongation (aminoacyl-tRNA⋅eEF1A), termination (eRF1⋅eRF3), and rescue (Pelota⋅Hbs1l). Comparative analyses reveal each factor exploits plasticity ribosomal center differentially remodel proteins rRNA. This leads varying...