Bickler Lab


The broad goal of the Bickler Laboratory is to understand how cells, organs and whole organisms respond and adapt to stress. The stresses we study are relevant to patients undergoing high-risk surgical procedures: reduced oxygen availability in blood and tissues, exposure to pharmacologic agents which profoundly alter cellular metabolism (such as anesthetics) and changes in temperature well beyond the physiological norm. The models that we use to advance this understanding are diverse: cells in culture, organotypic cultures of organs, hypoxia tolerant animals such as freshwater turtles and hibernating mammals, diving marine mammals, and human volunteer subjects in the laboratory, during deep dive simulations and at high altitude. In addition, we study patients undergoing complex neurological surgery. We believe that this “multispectral” approach to science is not only powerful but stimulating for our entire research group. 


Bickler Laboratory Currently Active Research Projects 

The following is a brief introduction to our current projects: 

1. Cellular and molecular biomarkers of hypoxia in human neurons. 
These studies have involved a diverse range of cellular models including cortical neurons from freshwater turtles, neural progenitor cells from Arctic ground squirrels and isolated cortical neurons from sea lions and elephant seals. We are primarily interested in the signaling pathways that exit in neurons that enable the cell to respond to hypoxia with an adaptive response that makes the cell more tolerant to subsequent severe hypoxic stress. The current model involves human neurons, derived from a neural progenitor cell line, and signaling pathways of the unfolded protein response (UPR), a system that regulates response to a wide variety of stresses. The UPR is a key player in preconditioning. 

2. Biomarkers for human adaptation to high altitude environments. 
Our laboratory has a long and storied history of high-altitude studies, dating to the early 1960’s when John Severinghaus defined the basic elements of how the human breathing control system changes at high altitude. We are currently working to understand how tissue oxygenation during exercise at high altitude causes the symptoms of acute mountain sickness, and relates to increases in inflammatory biomarkers such as cytokines. In addition, we are using deep RNA sequencing to identify biomarkers of hypoxia exposure, both to understand altitude adaptation and also as contrast to the impaired hypoxia adaptation that occurs in critically ill patients. 

3. Adaptation and injury of cells during hypothermia. 
Hypothermia has been an extremely potent experimental treatment for tissue ischemia, but clinical translation of hypothermia therapy has been disappointing. To address this conundrum, we have had a long interest in understanding the injurious effects of hypothermia and rewarming on neurons. These studies focus on the problem of protein misfolding and excitotoxicity which is found with mild hypothermia in developing rat hippocampus. 

4. Biomarkers predicting outcome following major spine surgery 
This project is driven by the perspective that current clinical monitors tell us little about tissue well-being during major surgery. Spine surgery involves large blood loss, hemodynamic changes, ICU admissions and a variety of adverse outcomes. We are testing whether adverse outcomes are predicted by changes in brain or muscle tissue oxygenation (near infrared spectroscopy) and circulating biomarkers such as small changes in cardiac troponins. 

5. Preconditioning and biomarkers in human cognitive preconditioning 
A major question in preconditioning science is whether humans can be preconditioned to improve clinical outcomes. We are testing the hypothesis that brief exposures to hypoxia or ischemia (blood pressure cuff on an extremity) can improve cognitive performance in humans. We will also identify small-molecule biomarkers related to the preconditioning effects. 

6. Brain oxygen in patients with cerebral vasospasm. 
Neurologic deterioration is common in survivors of brain hemorrhage. One of the causes of this problem is vasospasm in brain arteries. This can be treated by a neurointerventional radiology procedure of injecting a vasodilator such as verapamil into the affected vessels. A major limitation in caring for these patients is being able to continuously vasospasm, or a surrogate such as brain tissue oxygenation. We are testing whether cerebral oximetry can detect meaningful changes in brain oxygenation during treatment for vasospasm. 

7. Performance of clinical monitors that measure tissue oxygen, blood oxygen and dyshemoglobins. 
For decades, our laboratory has been a leading center for validation of monitors detecting oxyhemoglobin saturation in blood and tissues. We have protocols active for evaluating hypoxia, hypo and hypercarbia, detection of apnea, detection of anemia, presence of methemoglobin or carboxyhemoglobin and other conditions. 

8. Human dive physiology. 
Trained humans have astounding abilities to accomplish breath-hold dives. The physiology of these feats has been little studied. Our research team is developing methods and approaches to monitor divers and model gas exchange, brain blood flow and oxygen delivery during dive conditions and for the crucial period immediately after the first breath on re-surfacing. 

9. Novel treatments for snakebite. 
Snakebite is a neglected tropical disease, killing about 125,000 people in low and middle-income countries each year (see the video here). Current treatment with antivenins are expensive and snake-specific. We collaborate with Ophirex Inc. to understand the mechanisms involved in the benefit of the first near-universal antidote for snake-bite, small molecule inhibitors of venom and endogenous phospho-lipase A2. 

10. Global Health Technology Development. 
Development of safe, accurate and cost-effective medical monitors can improve the safety of surgery in developing countries. Driven by this imperative, we are involved in developing and testing a wide variety of novel medical monitors. Projects onfclude improving pulse oximeter performance in darkly pigmented patients, development of test methods for developing pulse oximeters that function well in patients with profound anemia, development of inexpensive CO2- monitoring for improving the safety of anesthesia, developing simple, non-invasive methods for detecting dyshemoglobins (such as carboxyhemoglobin and metHb, caused by carbon monoxide poisoning or exposure to nitrate fertilizers), and low-cost nerve stimulators for regional anesthesia. We have a number of partners in the UCSF Global Health community.




What is the Pulse-Ox network?

It's a large group of study-volunteers that participate in studies with our lab. Volunteers in our network routinely come back several times. The studies are generally pretty easy, pay well, and we try to have a good time.

If you want to join, read these bits of info and simply sign up below.
We pay you, you help advance the accuracy of non-invasive detectors, and we provide cookies and music during the studies.
Every couple of weeks or so, we announce new study dates. Volunteers registered with our network get notice of these dates, and first-come first served emails are allocated spots for the study days.
We generally run studies every other week, on Wednesdays and Thursdays.




What is a pulse oximeter anyway?

It's pictured above, and it's a non-invasive device that uses light to measure various physiologic variables. They've been around for 20 years, and principally they're used to easily measure the amount of oxygen O2 saturation in your blood.


What is involved in the study? 

This study pays $75-$100, and involves a little over an hour of your time. This study involves multiple breathing tests with brief, safe low levels of oxygen and withdrawal of 20-25 small blood samples (about 1.0 ml each). We withdraw these small samples via a wrist arterial catheter, which is inserted by the anesthesiologist under local anesthesia (lidocaine to numb the area). Total blood drawn during the study is about an ounce, or about 1/10th the blood you give when you donate.


What determines eligibility?

To participate, you must be a healthy non-smoker in good shape, between 18 to 50 years of age, without asthma, high or abnormally low blood pressure, diabetes, heart disease, lung disease, or obesity.


What is the methemoglobin study?

These are pretty cool, in fact. Here's why:
Methemoglobin is a cousin of hemoglobin, the protein in your blood that carries oxygen. Normally, hemoglobin's iron molecules are in the 2+ oxidation state: Fe2+. In this state, they carry oxygen. When another electron is knocked off, iron is further oxidized in the 3+ state: Fe3+.

This new state is what is called methemoglobin. It can no longer shuttle oxygen to your tissues. This is typicaly measured invasively, which is harder on the patient in addition to be a relatively slow method of detection. Not for long, though.....

Manufacturers are developing non-invasive devices similar to pulse-oximeters to detect the presence of methemoglobin. And it's all done quickly, without the need for needles. While these devices are being developed and tested, you can play a part in a study.


What's involved?

This study would require around 2 to 2.5 hours of your time, and it pays $200. To induce the formation of met-Hb in our study, a slow infusion of sodium nitrite is given via an intravenous line. Sodium nitrite oxidizes normal hemoglobin and produces methemoglobin. The nitrite infusion will slowly increase met-Hb in the blood from a normal level of .1%-1% to about 11%-13%. Levels of methemoglobin above this (above 20%) may cause fatigue, headache, exercise intolerance, dizziness, and mental status changes. Our study is not interested in these high levels, and at our levels we generally find volunteers report no observable changes.

Blood samples will be periodically drawn from an arterial line and analyzed in a co-oximeter, much like our usual pulse-ox studies. Upon initial infusion of the nitrite, your body already begins to metabolize methemoglobin back to normal hemoglobin. Once the study is complete, it will take around 2-4 hours for methemoglobin to drop to pre-study levels, so strenuous exercise immediately after the study is discouraged for a few hours.


What is Carboxyhemoglobin?

Carboxyhemoglobin is a complex formed by the binding of carbon monoxide and hemoglobin. This complex is formed in the human body when cabrbon monoxide is inhaled, most commonly from tobacco smoke. The formation of this complex can hinder the delivery of oxygen to your tissues.


What's involved?

This study would require around 2 to 2.5 hours of your time, and it pays $200. In our study, you will be given a very small, safe dose of carbon monoxide to inhale which will increase your carboxyhemoglobin levels to around 13%, approximately equivalent to smoking a pack of cigarettes. Some possible side effects include fatigue, or a feeling of light headedness. We will have pure oxygen on hand to reverse the effects if you feel any of those symptoms..

Throughout the study, we will periodically take 1cc sized blood samples from an arterial line which we will analyze in a co-oximeter machine. Those result will be compared with the results of a non-invasive oximeter, helping to determine it's accuracy. After the completion of the study, it will take between 4-6 hours for the carbon monoxide to leave your system so it is recommended that you not participate in any strenuous activity immediately after.


To join our network, simply email Laura Rhodes ([email protected]) in the Deptartment of Anesthesia.
For more information on our studies, please visit the hypoxialab.


The Pulse Oximeter Is Amazing, but Not Perfect.
Bickler P, Tremper KK. Anesthesiology. 2022 05 01; 136(5):670-671.

Neuroanatomical Basis for the Orexinergic Modulation of Anesthesia Arousal and Pain Control.
Xiang X, Chen Y, Li KX, Fang J, Bickler PE, Guan Z, Zhou W. Cell Neurosci. 2022; 16:891631.

Pulse Oximeter Performance, Racial Inequity, and the Work Ahead.
Okunlola O, Lipnick MS, Batchelder P, Bernstein M, Feiner J, Bickler P. Respir Care. 2021 Nov 12.

John W. Severinghaus, M.D., 1922 to 2021.
Bickler PE, Hornbein T, Saidman LJ. Anesthesiology. 2021 10 01; 135(4):555-557.

Association between tissue oxygenation and myocardial injury in patients undergoing major spine surgery: a prospective cohort study.
Bernholm KF, Meyhoff CS, Bickler P. BMJ Open. 2021 Sep 17; 11(9):e044342.

Extremes of age are associated with differences in the expression of selected pattern recognition receptor genes and ACE2, the receptor for SARS-CoV-2: implications for the epidemiology of COVID-19 disease.
Bickler SW, Cauvi DM, Fisch KM, Prieto JM, Sykes AG, Thangarajah H, Lazar DA, Ignacio RC, Gerstmann DR, Ryan AF, Bickler PE, De Maio A. BMC Med Genomics. 2021 05 24; 14(1):138.

Accuracy of Samsung Smartphone Integrated Pulse Oximetry Meets Full FDA Clearance Standards for Clinical Use.
Browne SH, Bernstein M, Bickler PE. medRxiv. 2021 Feb 18.

"Silent" Presentation of Hypoxemia and Cardiorespiratory Compensation in COVID-19.
Bickler PE, Feiner JR, Lipnick MS, McKleroy W. Anesthesiology. 2021 02 01; 134(2):262-269.

Amplification of Snake Venom Toxicity by Endogenous Signaling Pathways.
Bickler PE. Toxins (Basel). 2020 01 22; 12(2).

Intraoperative physiological ranges associated with improved outcomes after major spine surgery: an observational study.
Li G, Lin L, Xiao J, Rosenbaum S, Bickler P, Meng L. BMJ Open. 2019 05 28; 9(5):e025337.

Delayed LY333013 (Oral) and LY315920 (Intravenous) Reverse Severe Neurotoxicity and Rescue Juvenile Pigs from Lethal Doses of Micrurus fulvius (Eastern Coral Snake) Venom.
Lewin MR, Gilliam LL, Gilliam J, Samuel SP, Bulfone TC, Bickler PE, Gutiérrez JM. Toxins (Basel). 2018 Nov 17; 10(11).

Activation of orexin system facilitates anesthesia emergence and pain control.
Zhou W, Cheung K, Kyu S, Wang L, Guan Z, Kurien PA, Bickler PE, Jan LY. Toxins (Basel). Proc Natl Acad Sci U S A. 2018 11 06; 115(45):E10740-E10747.

Rescues Mice from Highly Neurotoxic, Lethal Doses of Papuan Taipan (Oxyuranus scutellatus) Venom.
Lewin MR, Gutiérrez JM, Samuel SP, Herrera M, Bryan-Quirós W, Lomonte B, Bickler PE, Bulfone TC, Williams DJ. Toxins (Basel). 2018 09 20; 10(10).

Response to Burtscher re: "Increased Cytokines at High Altitude: Lack of Effect of Ibuprofen on Acute Mountain Sickness, Physiological Variables, or Cytokine Levels".
Bickler P, Feiner JR, Lundeberg J. High Alt Med Biol. 2018 09; 19(3):304-305.

Developing Small Molecule Therapeutics for the Initial and Adjunctive Treatment of Snakebite.
Bulfone TC, Samuel SP, Bickler PE, Lewin MR. J. Trop Med. 2018; 2018:4320175.

Increased Cytokines at High Altitude: Lack of Effect of Ibuprofen on Acute Mountain Sickness, Physiological Variables, or Cytokine Levels.
J, Feiner JR, Schober A, Sall JW, Eilers H, Bickler PE. High Alt Med Biol. 2018 Sep; 19(3):249-258.

Four Types of Pulse Oximeters Accurately Detect Hypoxia during Low Perfusion and Motion.
Louie A, Feiner JR, Bickler PE, Rhodes L, Bernstein M, Lucero J.
Anesthesiology. 2018 03; 128(3):520-530.

Comparison of Transcranial Doppler and Ultrasound-Tagged Near Infrared Spectroscopy for Measuring Relative Changes in Cerebral Blood Flow in Human Subjects.
Lipnick MS, Cahill EA, Feiner JR, Bickler PE.
Anesth Analg. 2018 Feb;126(2):579-587.

Effects of Changes in Arterial Carbon Dioxide and Oxygen Partial Pressures on Cerebral Oximeter Performance.
Schober A, Feiner JR, Bickler PE, Rollins MD.
Anesthesiology. 2018 Jan;128(1):97-108.

Little Black Boxes: Noncardiac Implantable Electronic Medical Devices and Their Anesthetic and Surgical Implications.
Srejic U, Larson P, Bickler PE.
Anesth Analg. 2017 Jul;125(1):124-138.

Reduction in N-methyl-D-aspartate Receptor-mediated Cell Death in Hippocampal Neurons by Glucose Reduction Preconditioning.
Yang N, Gabatto P, Bickler PE.
J Neurosurg Anesthesiol. 2017 Oct;29(4):448-457.

Interaction of Isoflurane, Tumor Necrosis Factor-α and β-Amyloid on Long-term Potentiation in Rat Hippocampal Slices.
Zhou R, Bickler P.
Anesth Analg. 2017 Feb;124(2):582-587.

Varespladib (LY315920) Appears to Be a Potent, Broad-Spectrum, Inhibitor of Snake Venom Phospholipase A2 and a Possible Pre-Referral Treatment for Envenomation.
Lewin M, Samuel S, Merkel J, Bickler P.
Toxins (Basel). 2016 Aug 25;8(9).

Trends and Challenges in Clinical Monitoring: Papers From the 2015 IAMPOV Symposium.
Bickler PE, Cannesson M, Shelley KH.
Anesth Analg. 2017 Jan;124(1):2-3. No abstract available. 

Effects of Acute, Profound Hypoxia on Healthy Humans: Implications for Safety of Tests Evaluating Pulse Oximetry or Tissue Oximetry Performance.
Bickler PE, Feiner JR, Lipnick MS, Batchelder P, MacLeod DB, Severinghaus JW.
Anesth Analg. 2017 Jan;124(1):146-153. Review.

Enough Information to Evaluate Clinical Monitors?
Bickler PE.
Anesth Analg. 2016 Jul;123(1):254-5.

Tissue Oximetry and Clinical Outcomes.
Bickler P, Feiner J, Rollins M, Meng L.
Anesth Analg. 2017 Jan;124(1):72-82. Review.

The Accuracy of Pulse Spectroscopy for Detecting Hypoxemia and Coexisting Methemoglobin or Carboxyhemoglobin.
Kulcke A, Feiner J, Menn I, Holmer A, Hayoz J, Bickler P.
Anesth Analg. 2016 Jun;122(6):1856-65.

The Accuracy of 6 Inexpensive Pulse Oximeters Not Cleared by the Food and Drug Administration: The Possible Global Public Health Implications.
Lipnick MS, Feiner JR, Au P, Bernstein M, Bickler PE.
Anesth Analg. 2016 Aug;123(2):338-45.

Hypoxic preconditioning and cell death from oxygen/glucose deprivation co-opt a subset of the unfolded protein response in hippocampal neurons.
Bickler PE, Clark JP, Gabatto P, Brosnan H.
Neuroscience. 2015 Dec 3;310:306-21.

Reversal of experimental paralysis in a human by intranasal neostigmine aerosol suggests a novel approach to the early treatment of neurotoxic envenomation.
Lewin MR, Bickler P, Heier T, Feiner J, Montauk L, Mensh B.
Clin Case Rep. 2013 Oct;1(1):7-15.

Early Treatment with Intranasal Neostigmine Reduces Mortality in a Mouse Model of Naja naja (Indian Cobra) Envenomation.
Lewin MR, Samuel SP, Wexler DS, Bickler P, Vaiyapuri S, Mensh BD.
J Trop Med. 2014;2014:131835. doi: 10.1155/2014/131835. Epub 2014 May 14.

Limitations of Mild, Moderate, and Profound Hypothermia in Protecting Developing Hippocampal Neurons After Simulated Ischemia.
Gregersen M, Lee DH, Gabatto P, Bickler PE.
Ther Hypothermia Temp Manag. 2013 Dec 1;3(4):178-188.

Factors affecting the performance of 5 cerebral oximeters during hypoxia in healthy volunteers.
Bickler PE, Feiner JR, Rollins MD.
Anesth Analg. 2013 Oct;117(4):813-23. doi: 10.1213/ANE.0b013e318297d763. Epub 2013 Sep 10.

Accuracy of the Lifebox pulse oximeter during hypoxia in healthy volunteers.
Dubowitz G, Breyer K, Lipnick M, Sall JW, Feiner J, Ikeda K, MacLeod DB, Bickler PE.
Anaesthesia. 2013 Dec;68(12):1220-3. doi: 10.1111/anae.12382. Epub 2013 Aug 31.

Xenon neurotoxicity in rat hippocampal slice cultures is similar to isoflurane and sevoflurane.
Brosnan H, Bickler PE.
Anesthesiology. 2013 Aug;119(2):335-44

Reversal of experimental paralysis in a human by intranasal neostigmine aerosol suggests a novel approach to the early treatment of neurotoxic envenomation. 
Lewin MR, Bickler P, Heier T, Feiner J, Montauk L, Mensh B. 
Clin Case Rep. 2013 Oct;1(1):7-15. doi: 10.1002/ccr3.3. Epub 2013 Jul 24.

Early Treatment with Intranasal Neostigmine Reduces Mortality in a Mouse Model of Naja naja (Indian Cobra) Envenomation. 
Lewin MR, Samuel SP, Wexler DS, Bickler P, Vaiyapuri S, Mensh BD.
J Trop Med. 2014;2014:131835. doi: 10.1155/2014/131835. Epub 2014 May 14.

Limitations of Mild, Moderate, and Profound Hypothermia in Protecting Developing Hippocampal Neurons After Simulated Ischemia.
Gregersen M, Lee DH, Gabatto P, Bickler PE.
Ther Hypothermia Temp Manag. 2013 Dec 1;3(4):178-188.PM

Factors affecting the performance of 5 cerebral oximeters during hypoxia in healthy volunteers.
Bickler PE, Feiner JR, Rollins MD.
Anesth Analg. 2013 Oct;117(4):813-23. doi:

Accuracy of the Lifebox pulse oximeter during hypoxia in healthy volunteers.
Dubowitz G, Breyer K, Lipnick M, Sall JW, Feiner J, Ikeda K, MacLeod DB, Bickler PE.
Anaesthesia. 2013 Dec;68(12):1220-3. doi: 10.1111/anae.12382. Epub 2013 Aug 31.

Xenon neurotoxicity in rat hippocampal slice cultures is similar to isoflurane and sevoflurane.
Brosnan H, Bickler PE.
Anesthesiology. 2013 Aug;119(2):335-44. doi:

Accuracy of carboxyhemoglobin detection by pulse CO-oximetry during hypoxemia
Feiner JR, Rollins MD, Sall JW, Eilers H, Au P, Bickler PE.
Anesth Analg. 2013 Oct;117(4):847-58. doi:

Propofol at clinically relevant concentrations increases neuronal differentiation but is not toxic to hippocampal neural precursor cells in vitro.
Sall JW, Stratmann G, Leong J, Woodward E, Bickler PE.
Anesthesiology. 2012 Nov;117(5):1080-90. doi:

Anesthetic protection of neurons injured by hypothermia and rewarming: roles of intracellular Ca2+ and excitotoxicity.
Bickler PE, Warren DE, Clark JP, Gabatto P, Gregersen M, Brosnan H.
Anesthesiology. 2012 Aug;117(2):280-92.

Delayed environmental enrichment reverses sevoflurane-induced memory impairment in rats.
Shih J, May LD, Gonzalez HE, Lee EW, Alvi RS, Sall JW, Rau V, Bickler PE, Lalchandani GR, Yusupova M, Woodward E, Kang H, Wilk AJ,
Carlston CM, Mendoza MV, Guggenheim JN, Schaefer M, Rowe AM, Stratmann G.
Anesthesiology. 2012 Mar;116(3):586-602. doi: 10.1097/ALN.0b013e318247564d.

The emergence level of the musculocutaneous nerve from the brachial plexus: implications for infraclavicular nerve blocks.
Pianezza A, Salces y Nedeo A, Chaynes P, Bickler PE, Minville V.
Anesth Analg. 2012 May;114(5):1131-3. doi: 10.1213/ANE.0b013e3182498643. Epub 2012 Feb 6.

Hypothermia and rewarming injury in hippocampal neurons involve intracellular Ca2+ and glutamate excitotoxicity.
Warren DE, Bickler PE, Clark JP, Gregersen M, Brosnan H, McKleroy W, Gabatto P.
Neuroscience. 2012 Apr 5;207:316-25. doi: 10.1016/j.neuroscience.2011.12.034. Epub 2012 Jan 12.

Hypoxic preconditioning failure in aging hippocampal neurons: impaired gene expression and rescue with intracellular calcium chelation.
Bickler PE, Fahlman CS, Gray JJ.
J Neurosci Res. 2010 Dec;88(16):3520-9. doi: 10.1002/jnr.22508. Epub 2010 Oct 8.

Improved accuracy of methemoglobin detection by pulse CO-oximetry during hypoxia.
Feiner JR, Bickler PE.
Anesth Analg. 2010 Nov;111(5):1160-7. doi: 10.1213/ANE.0b013e3181f46da8. Epub 2010 Sep 14.

Perioperative hypothermia (33 degrees C) does not increase the occurrence of cardiovascular events in patients undergoing cerebral aneurysm surgery: findings from the Intraoperative Hypothermia for Aneurysm Surgery Trial.
Nguyen HP, Zaroff JG, Bayman EO, Gelb AW, Todd MM, Hindman BJ; IHAST-MIDS and IHAST Investigators.
Anesthesiology. 2010 Aug;113(2):327-42. doi: 10.1097/ALN.0b013e3181dfd4f7.

Enhanced hypoxic preconditioning by isoflurane: signaling gene expression and requirement of intracellular Ca2+ and inositol triphosphate receptors.
Bickler PE, Fahlman CS.
Brain Res. 2010 Jun 22;1340:86-95. doi: 10.1016/j.brainres.2010.04.059. Epub 2010 Apr 29.

Antifreeze protein suppresses spontaneous neural activity and protects neurons from hypothermia/re-warming injury.
Rubinsky L, Raichman N, Lavee J, Frenk H, Ben-Jacob E, Bickler PE.
Neurosci Res. 2010 Jul;67(3):256-9. doi: 10.1016/j.neures.2010.04.004. Epub 2010 Apr 14.

Erythropoietin promotes hippocampal neurogenesis in in vitro models of neonatal stroke.
Osredkar D, Sall JW, Bickler PE, Ferriero DM.
Neurobiol Dis. 2010 May;38(2):259-65. doi: 10.1016/j.nbd.2010.01.015. Epub 2010 Feb 1.

Isoflurane does not affect brain cell death, hippocampal neurogenesis, or long-term neurocognitive outcome in aged rats.
Stratmann G, Sall JW, Bell JS, Alvi RS, May Ld, Ku B, Dowlatshahi M, Dai R, Bickler PE, Russell I, Lee MT, Hrubos MW, Chiu C.
Anesthesiology. 2010 Feb;112(2):305-15. doi: 10.1097/ALN.0b013e3181ca33a1.

Accuracy of methemoglobin detection by pulse CO-oximetry during hypoxia.
Feiner JR, Bickler PE, Mannheimer PD.
Anesth Analg. 2010 Jul;111(1):143-8. doi: 10.1213/ANE.0b013e3181c91bb6. Epub 2009 Dec 10.

No association between intraoperative hypothermia or supplemental protective drug and neurologic outcomes in patients undergoing temporary clipping during cerebral aneurysm surgery: findings from the Intraoperative Hypothermia for Aneurysm Surgery Trial.
Hindman BJ, Bayman EO, Pfisterer WK, Torner JC, Todd MM; IHAST Investigators.
Anesthesiology. 2010 Jan;112(1):86-101. doi: 10.1097/ALN.0b013e3181c5e28f.

Expression of signal transduction genes differs after hypoxic or isoflurane preconditioning of rat hippocampal slice cultures.
Bickler PE, Fahlman CS.
Anesthesiology. 2009 Aug;111(2):258-66.

Consensus statement: first international workshop on anesthetics and Alzheimer's disease.
Baranov D, Bickler PE, Crosby GJ, Culley DJ, Eckenhoff MF, Eckenhoff RG, Hogan KJ, Jevtovic-Todorovic V, Palotás A, Perouansky M, Planel E,
Silverstein JH, Wei H, Whittington RA, Xie Z, Zuo Z.
Anesth Analg. 2009 May;108(5):1627-30.

Isoflurane inhibits growth but does not cause cell death in hippocampal neural precursor cells grown in culture.
Sall JW, Stratmann G, Leong J, McKleroy W, Mason D, Shenoy S, Pleasure SJ, Bickler PE.
Anesthesiology. 2009 Apr;110(4):826-33.

Inositol 1,4,5-triphosphate receptors and NAD(P)H mediate Ca(2+) signaling required for hypoxic preconditioning of hippocampal neurons.
Bickler PE, Fahlman CS, Gray J, McKleroy W.
Neuroscience. 2009 Apr 21;160(1):51-60. Epub 2009 Feb 13.

Effect of nitrous oxide use on long-term neurologic and neuropsychological outcome in patients who received temporary proximal artery occlusion during cerebral aneurysm clipping surgery.
Pasternak JJ, McGregor DG, Lanier WL, Schroeder DR, Rusy DA, Hindman B, Clarke W, Torner J, Todd MM; IHAST Investigators.
Anesthesiology. 2009 Mar;110(3):563-73.

Arctic ground squirrel (Spermophilus parryii) hippocampal neurons tolerate prolonged oxygen-glucose deprivation and maintain baseline ERK1/2 and JNK activation despite drastic ATP loss.
Christian SL, Ross AP, Zhao HW, Kristenson HJ, Zhan X, Rasley BT, Bickler PE, Drew KL.
J Cereb Blood Flow Metab. 2008 Jul;28(7):1307-19. Epub 2008 Apr 9.

Dark skin decreases the accuracy of pulse oximeters at low oxygen saturation: the effects of oximeter probe type and gender. Feiner JR, Severinghaus JW, Bickler PE.
Anesth Analg. 2007 Dec;105(6 Suppl):S18-23, tables of contents.

Hypoxia tolerance in reptiles, amphibians, and fishes: life with variable oxygen availability.
Bickler PE, Buck LT. Annu Rev Physiol. 2007;69:145-70. Review.



Philip E. Bickler, MD, PhD

Professor of Anesthesia

Dr. Philip E. Bickler received his Bachelors Degree in Biology at UC Riverside in 1977. He attended graduate school at UCLA, receiving a PhD in Biology in 1981. From there he went to Scripps Institution of Oceanography as an NSF and NIH postdoctoral fellow from 1981-1983 where he studied acid-base balance in hibernation. During Medical School at UCSD (1983-1986) he worked with Frank Powell in the Dept. of Medicine on Intrapulmonary Shunts in Duck Lungs and Alligators. In 1986 he moved to UCSF to work with John Severinghaus. He went on to complete his Anesthesiology residency at UCSF and he has been a faculty member there since 1991.

He lives with his family of a wife, three children and one chocolate labrador in Larkspur, across the Golden Gate Bridge from San Francisco.


Laura Rhodes

Clinical Research Coordinator
Department Of Anesthesia & Perioperative Care
University Of California, San Francisco

Laura joined the lab in April 2015 as the new Clinical Research Coordinator.  Following completion of her psychology degree at UCSC in 2007, Laura began her career in research with the UCSF Memory and Aging Center, and has since worked coordinating projects for various research indications throughout the San Francisco Bay Area, including dementia, cognition, neuroimaging, social functioning, PTSD, schizophrenia, and other CNS focused clinical trials.  She also has a background in public health research focused on tobacco and alcohol policy work and training in EMS.  Her interest in clinical research design and improving patient outcomes led her to find the Hypoxia Lab, where she is excited to learn more about device development and assist in expanding the labs’ research projects.  She is also currently pursuing a graduate degree in Health Policy and Law at UCSF.  Laura’s main roles in the lab are coordinating study subjects, assisting during studies, and maintaining all regulatory documents necessary for clinical research in accordance with good clinical practices. For more information on scheduling or regulatory requests, please complete the appropriate contact form or email her at [email protected]


Michael Lipnick, M.D.

Assistant Professor
Department Of Anesthesia & Perioperative Care
University Of California, San Francisco

Michael Lipnick MD is an Assistant Professor in the Department of Anesthesia at UCSF and based clinically at San Francisco General Hospital. He is a graduate of the UCSF School of Medicine and completed residency programs in Internal Medicine at Harvard’s Brigham and Women’s Hospital and Anesthesia Residency at UCSF as well as Critical Care Fellowship at UCSF.  His research interests include comparative physiology with focus on mechanisms of hypoxia tolerance and preconditioning. He completed a research fellowship at Stanford’s Hopkins Marine Station where he studied mechanisms of cold-tolerance among endothermic fish. Michael’s interests in public health have focused on injury and critical care in resource-constrained settings. He has served as a contributor to the Global Burden of Disease Study Group and co-founded The Global Health Hub ( and Global Partners in Anesthesia and Surgery (GPAS –  Dr. Lipnick’s current grant funding is aimed at developing novel methods for oximetry validation during severe anemia.


Koa Gudelunas

Research Assistant
Department Of Anesthesia & Perioperative Care
Department Of Physiological Nursing
University Of California, San Francisco/ San Francisco VA Medical Center

Koa joined the lab in May 2016.  His research projects in the lab include the value of cerebral tissue oxygenation during Neurovascular surgery and its potential use as a way to predict surgical outcomes and if cerebral oximetry can better access cerebral perfusion during Neurosurgery.  He also has interests in heart rate variability as a predictor of cardiac arrest. He received his B.S. in Neuroscience from The University of California, Santa Cruz in 2015.  His ultimate goal is to practice medicine and plans to apply to medical school in the next couple years.


Maribel Pineda, BS

Administrative Assistant

Maribel was born in Nicaragua but raised in San Francisco.  She joined the Bickler group in October 2008 and provides administrative support for the lab.  In addition to supporting Dr. Bickler’s lab, Maribel also supports six other anesthesia labs and has been working at UCSF since December 1999. She brings decades of experience of working in both the academic and private sectors of research, clinical, and financial areas.  
Maribel treasures her weekends and is a Big Fan of the warm weather and beaches and anything involved in most outdoor activities.  Dancing and music are up there, too!


Katrine Burnholm

Katrine Feldballe Bernholm
Visiting Research Scholar
Department of Anesthesia and Perioperative Care
University Of California, San Francisco

Katrine is a Danish medical student from the University of Copenhagen. She is here on a scholarship bringing Danish medical students to the Bay Area ( She joined the lab in August 2017 and will for 10 months be working on different projects in the Bickler Lab. Her primary focus will be her research project investigating the association between intra-operative tissue oxygenation and post-operative clinical outcome in patients undergoing spine surgery at UCSF. A special interest is post-operative myocardial injury in this group of patients, which will be assessed by troponin in plasma. General interests are intensive care and improvement of perioperative care. Katrine expect to graduate from medical school in June 2019 and pursue a career in anesthesia and intensive care, possibly including a PhD along the way. 

Odmara Barreto Chang, MD, PhD

Clinical Instructor





Andrew Schober, M.D.

Assistant Clinical Professor





Harpreet Kaur

Research Assistant 

Harpreet joined the Bickler Lab in December 2017. She is an Undergraduate Visiting Scholar from San Francisco State University. In May 2018 she will receive her B.S. in Biology with concentration in Physiology. She volunteers in the lab as a research assistant and is currently involved in a study investigating ‘The Effects of Hypoxia and Preconditioning on Cognitive Function’ with Dr. Odmara Barreto Chang. Harpreet is currently focused on pre-med coursework; her long term goals include attending graduate school and practicing medicine.


















Philip E. Bickler MD, PhD
Professor of Anesthesia
University of California at San Francisco
Sciences Building, Room S-257, Box 0542
513 Parnassus Ave.
San Francisco, CA 94143-0542
Phone: 415 476-1411
Fax: 415 476-8841
Email: [email protected]

For inquiries about conducting a pulse oximeter validation study, contact our clinical research coordinator:

Laura Rhodes
Clinical Research Coordinator
Phone: 415-476-1412
Email: [email protected]