Bio

Current Role at Stanford


I joined the Cardiopulmonary Research Program of Drs. Rabinovitch and Bland at Stanford University in 2002, as the Academic and Research Program Officer. Additionally, in 2005-2015, I was the Administrative Coordinator of the Cardiovascular and Pulmonary Science Scholarly Concentration for medical students at Stanford University School of Medicine. This included facilitating communication of the co-Directors with the School of Medicine Administration, the medical students, and the faculty mentors, and coordination of the MED223 course. I organize the educational activities of the lab, including a major role in developing the Cardiopulmonary Research in Progress Seminar Series, and assist the faculty and fellows with the preparation of grant proposals, IRB, APLAC and Biosafety protocols, manuscripts, and presentations. I serve as the Site Coordinator for the Stanford Transplant Procurement Center of the Pulmonary Hypertension Breakthrough Initiative (PHBI), headed by Dr Rabinovitch, and in this capacity, I oversee patient recruitment, data collection and reporting, and ensure compliance with university and federal guidelines. I am the coordinator for two NIH/NHLBI training programs: the K12 Career Development Program in "Omics of Lung Diseases" (PIs: M Rabinovitch, M Nicolls and M Snyder), and for the Stanford Cardiovascular Institute (CVI) T32 Training Program "Mechanisms and Innovation Vascular Disease" (PIs: R Dalman and P Tsao).

Supervisors


Honors & Awards


  • Chaim Weizmann Fellowship for postdoctoral studies, Chaim Weizmann Fellowship Committee, Israel (1990)
  • Feinberg Graduate School Distinction Award for Ph.D. students, Weizmann Institute of Science, Rehovot, Israel (1990)
  • Wolf Foundation Scholarship for Ph.D. students, Weizmann Institute of Science, Rehovot, Israel (1987)
  • Fellow, Netherlands-Israel Foreign Ministry Student Exchange Program (Univ of Groningen), Netherlands-Israel Foreign Ministry Student Exchange Program (1984-1985)
  • Feinberg Graduate School Special Distinction Award for M.Sc. students, Weizmann Institute of Science, Rehovot, Israel (1983)

Education & Certifications


  • Certificate, Wharton School of Business, University of Pennsylvania, Philadelphia, PA, Business Administration (2000)
  • Post Doctoral training, University of Pennsylvania School of Medicine, Philadelphia, PA, Physiology (1996)
  • PhD, The Weizmann Institute of Science, Rehovot, Israel, Life Sciences (Thesis research carried out at the Department of Physical Chemistry and the department of Biochemistry) (1990)
  • MSc, The Weizmann Institute of Science, Rehovot, Israel, Life Sciences (1983)
  • BSc, The Hebrew University of Jerusalem, Jerusalem, Israel, Chemistry (1980)

Service, Volunteer and Community Work


  • Sequoia High School Education Foundation Board Member, Sequoia High School (7/1/2011 - Present)

    Corresponding Secretary

    Location

    Redwood City, CA

  • Cipriani After School Care, Board Member, Cipriani After School Care (9/1/2006 - 7/1/2009)

    Site Representative and Board Member

    Location

    Belmont, CA

  • Peninsula Temple Beth El, RS Board/Education Committee Member, Peninsula Temple Beth El (6/1/2006 - 6/1/2008)

    Location

    San Mateo, CA

Professional

Work Experience


  • Associate Director - Scientific Development Administrator, Institute for Medicine and Engineering (IME), University of Pennsylvania (7/1/1996 - 6/15/2002)

    Location

    Philadelphia, PA

  • Teaching Assistant, Teaching Assistant, The Faculty of Agriculture, Hebrew Univ. of Jerusalem, Rehovot, Israel (10/1/1988 - 5/1/1990)

    Teaching assistant, Chemistry for undergraduate students

    Location

    Rehovot, Israel

Publications

All Publications


  • On-line studies of activation events in primary human T lymphocytes. ImmunoMethods BENTAL, M., DEUTSCH, C. 1994; 4 (2): 148-162

    Abstract

    In this paper, we review our NMR studies of human peripheral blood T lymphocytes. These studies focus on the physiological and biochemical alterations accompanying cell cycle progression. In particular, we have characterized phosphorus metabolism, glucose utilization and lactate production, and pH regulation using 31P, 13C, and 19F NMR, respectively. These studies required developing new methods for monitoring on-line stimulation of quiescent T cells under sterile, physiological conditions (i.e., CO2/HCO3- buffer, 37 degrees C) for prolonged periods of time. A perfusion system optimized for T lymphocytes inside agarose beads is described. In addition, custom-designed 19F NMR pH indicators were synthesized, characterized, and used to determine intracellular pH in quiescent lymphocytes, stimulated lymphocytes, and lymphocytes undergoing the G0-G1 transition. These unique molecular probes are described in detail. Finally, the physiological relevance of our findings regarding carbon metabolism and pH regulation is considered in the context of mitogenesis.

    View details for PubMedID 8069534

  • F-19-NMR STUDY OF PRIMARY HUMAN T-LYMPHOCYTE ACTIVATION - EFFECTS OF MITOGEN ON INTRACELLULAR PH AMERICAN JOURNAL OF PHYSIOLOGY BENTAL, M., DEUTSCH, C. 1994; 266 (2): C541-C551

    Abstract

    Intracellular pH of purified human T lymphocytes was studied using nuclear magnetic resonance (NMR) spectroscopy under physiological conditions. In this paper we introduce a new improved 19F-NMR pH probe, 2-amino-3,3'-difluoroisobutyric acid (vic-difluoro-alpha-methylalanine), which has a pKa of approximately 7.0, sensitivity of 0.83 ppm/pH, is noncytotoxic, and provides better signal-to-noise ratio for intracellular pH determinations. Quiescent and stimulated lymphocytes display different homeostatic intracellular pH values. Quiescent cells maintain intracellular pH of 7.04 +/- 0.03 at extracellular pH values between 6.9 and 7.3, and stimulated cells maintain intracellular pH of 7.25 +/- 0.05 at extracellular pH values between 7.0 and 7.5. Stimulation with ionomycin plus phorbol 12-myristate 13-acetate leads to intracellular alkalinization within 90 min, reaching the more alkaline steady-state value of 7.25 within 7-10 h. Proliferation, but not viability, of lymphocytes is dependent on extracellular pH in the range of 6.4-8.0, and this dependence is not due to limiting interleukin-2 elaboration. The mechanisms of pH regulation and the possible implications of a permissive pH for T lymphocyte proliferation are discussed.

    View details for Web of Science ID A1994NA80100028

    View details for PubMedID 8141269

  • METABOLIC CHANGES IN ACTIVATED T-CELLS - AN NMR-STUDY OF HUMAN PERIPHERAL-BLOOD LYMPHOCYTES MAGNETIC RESONANCE IN MEDICINE BENTAL, M., DEUTSCH, C. 1993; 29 (3): 317-326

    Abstract

    Using NMR spectroscopy, we studied purified, human T lymphocytes in a serum-free medium. Purified cells were entrapped inside agarose beads and induced to proliferate by the mitogens phorbol-12-myristate-13-acetate and ionomycin. T lymphocytes in standard culture and inside agarose beads exhibit comparable viability, and similar extent and kinetics of DNA synthesis and interleukin-2 secretion. 31P-NMR revealed decreased phosphomonoester and increased phosphodiester content in cells stimulated for two days or longer. 13C-glucose utilization and 13C-lactate production rates showed that 85% of the utilized glucose was converted to lactate. 1H-NMR spectra of the perfusing media indicated that lactate was also produced from substrates other than glucose or glycogen. Glucose accounted for 25% of the lactate produced by quiescent cells, and for 67% of lactate production by stimulated cells. Glycolysis was enhanced 6-fold within the first 2 hours following stimulation, and 15-fold by 48 or 96 h. Aerobic lactate production was increased 3-fold by 48 h, with only a minor enhancement during the first 12 h of stimulation. Our results indicate a shift from mostly aerobic to mostly anaerobic lactate production in T lymphocytes within the first 90 min of the G0 to G1 transition during cell cycle progression.

    View details for Web of Science ID A1993KQ35800006

    View details for PubMedID 8450740

  • HYDROLYSIS OF POLYPHOSPHATES AND PERMEABILITY CHANGES IN RESPONSE TO OSMOTIC SHOCKS IN CELLS OF THE HALOTOLERANT ALGA DUNALIELLA PLANT PHYSIOLOGY Weiss, M., BENTAL, M., Pick, U. 1991; 97 (3): 1241-1248

    Abstract

    The effects of osmotic shocks on polyphosphates and on the vacuolar fluorescent indicator atebrin have been investigated to test whether acidic vacuoles in the halotolerant alga Dunaliella salina have a role in osmoregulation. Upshocks and downshocks induce different patterns of polyphosphate hydrolysis. Upshocks induce rapid formation of new components, tentatively identified as 5 or 6 linear polyphosphates, formed only after upshocks with NaCl and not with glycerol, indicative of compartmentation of Na(+) into the vacuoles. Conversely, downshocks induce a slower transient accumulation of tripolyphosphates, indicating activation of a different hydrolytic process within the vacuoles. Osmotic shocks do not lead to release of atebrin from acidic vacuoles, indicating that they do not induce a major intravacuolar alkalinization. However, osmotic shocks induce transient permeability changes measured by amine-induced atebrin release from vacuoles. Hypoosmotic shocks transiently increase the permeability (up to 20-fold), whereas hyperosmotic shocks induce a rapid drop in permeability. Electron micrographs of osmotically shocked cells also reveal transient changes in the surface and internal organelles of D. salina cells. It is suggested that hyperosmotic and hypoosmotic shocks induce different changes within acidic vacuoles and in the organization and/or composition of the plasma membrane in Dunaliella.

    View details for Web of Science ID A1991GT79900054

    View details for PubMedID 16668515

  • INVIVO PH REGULATION BY A NA+/H+ ANTIPORTER IN THE HALOTOLERANT ALGA DUNALIELLA-SALINA PLANT PHYSIOLOGY Katz, A., BENTAL, M., Degani, H., AVRON, M. 1991; 96 (1): 110-115

    Abstract

    Na(+)/H(+) exchange activity in whole cells of the halotolerant alga Dunaliella salina can be elicited by intracellular acidification due to addition of weak acids at appropriate external pH. The changes in both intracellular pH and Na(+) were followed. Following a mild intracellular acidification, intracellular Na(+) content increased dramatically and then decreased. We interpret the phase of Na(+) influx as due to the activation of the plasma membrane Na(+)/H(+) antiporter and the phase of Na(+) efflux as due to an active Na(+) extrusion process. The following observations are in agreement with this interpretation: (a) the Na(+) influx phase was sensitive to Li(+), which is an inhibitor of the Na(+)/H(+) antiporter, did not require energy, and was insensitive to vanadate; (b) the Na(+) efflux phase is energy-dependent and sensitive to the plasma membrane ATPase inhibitor, vanadate. Following intracellular acidification, a drastic decrease in the intracellular ATP content is observed that is reversed when the cells regain their neutral pH value. We suggest that the intracellular acidification-induced change in the internal Na(+) concentration is due to a combination of Na(+) uptake via the Na(+)/H(+) antiporter and an active, ATPase-dependent, Na(+) extrusion. The Na(+)/H(+) antiporter seems, therefore, to play a principal role in internal pH regulation in Dunaliella.

    View details for Web of Science ID A1991FN15700017

    View details for PubMedID 16668138

  • POLYPHOSPHATE METABOLISM IN THE ALGA DUNALIELLA-SALINA STUDIED BY P-31-NMR BIOCHIMICA ET BIOPHYSICA ACTA BENTAL, M., Pick, U., AVRON, M., Degani, H. 1991; 1092 (1): 21-28

    Abstract

    Polyphosphate synthesis and the state of the intracellular polyphosphates in the unicellular green alga Dunaliella salina were studied using in vivo 31P-NMR spectroscopy. By perfusing phosphate-depleted algal cells trapped inside agarose beads with orthophosphate (Pi) containing medium, we were able to follow the process of polyphosphate synthesis in whole, living cells. The results suggest that, in Dunaliella, low molecular weight, probably cyclic, polyphosphate intermediates are synthesized from Pi, and are then condensed to high molecular weight polymers. Studies of the intracellular organization of the polyphosphates by electron microscopy and solid-state NMR techniques indicate that most of these polymers are stored in the cell in a soluble form, and not in solid-like structures.

    View details for Web of Science ID A1991FF14500004

    View details for PubMedID 2009308

  • POLYPHOSPHATE-HYDROLYSIS - A PROTECTIVE MECHANISM AGAINST ALKALINE STRESS FEBS LETTERS Pick, U., BENTAL, M., CHITLARU, E., Weiss, M. 1990; 274 (1-2): 15-18

    Abstract

    Different microorganisms, including yeast and algae, accumulate large amounts of polyphosphates. However, the physiological role of polyphosphates is largely unknown. In vivo 31P NMR studies, carried out in the unicellular alga, Dunaliella salina, demonstrate the cytoplasmic alkalization induces massive hydrolysis of polyphosphates, which is correlated kinetically with the recovery of cytoplasmic pH. Analysis of acid extracts of the cells indicates that long-chain polyphosphates are hydrolysed mainly to tripolyphosphate. It is suggested that the hydrolysis of polyphosphates provides a pH-stat mechanism to counterbalance alkaline stress.

    View details for Web of Science ID A1990EK67600004

    View details for PubMedID 2253767

  • THE ROLE OF INTRACELLULAR ORTHOPHOSPHATE IN TRIGGERING OSMOREGULATION IN THE ALGA DUNALIELLA-SALINA EUROPEAN JOURNAL OF BIOCHEMISTRY BENTAL, M., Pick, U., AVRON, M., Degani, H. 1990; 188 (1): 117-122

    Abstract

    A new hypothesis is presented for the mechanism of metabolic response during osmoregulation in the alga Dunaliella salina. We propose that the osmotic response is initiated by differential volume changes of the cytoplasm and the chloroplast (observed using the electron microscope) which alter the cytoplasmic orthophosphate concentration. This triggers a flow through the Pi/triose-phosphate shuttle, activating chloroplast enzymes in the direction of either starch or glycerol synthesis. The Pi-dependent response was investigated in vivo using NMR. The rates of glycerol synthesis or elimination following osmotic shocks were modulated by the intracellular Pi level as predicted by the hypothesis.

    View details for Web of Science ID A1990CR20900016

    View details for PubMedID 2318197

  • METABOLIC STUDIES WITH NMR-SPECTROSCOPY OF THE ALGA DUNALIELLA-SALINA TRAPPED WITHIN AGAROSE BEADS EUROPEAN JOURNAL OF BIOCHEMISTRY BENTAL, M., Pick, U., AVRON, M., Degani, H. 1990; 188 (1): 111-116

    Abstract

    A technique for the entrapment of the unicellular algae Dunaliella salina in agarose beads and their perfusion during NMR measurements is presented. The trapped cells maintained their ability to proliferate under normal growth conditions, and remained viable and stable under steady-state conditions for long periods during NMR measurements. Following osmotic shock in the dark, prominent changes were observed in the intracellular level of ATP and polyphosphates, but little to no changes in the intracellular pH or orthoposphate content. When cells were subjected to hyperosmotic shock, the ATP level decreased. The content of NMR-visible polyphosphates decreased as well, presumably due to the production of longer, NMR-invisible structures. Following hypoosmotic shock, the ATP content increased and longer polyphosphates were broken down to shorter, more mobile polymers.

    View details for Web of Science ID A1990CR20900015

    View details for PubMedID 2318196

  • NA-23-NMR STUDIES OF THE INTRACELLULAR SODIUM-ION CONCENTRATION IN THE HALOTOLERANT ALGA DUNALIELLA-SALINA PLANT PHYSIOLOGY BENTAL, M., Degani, H., AVRON, M. 1988; 87 (4): 813-817

    Abstract

    The Intracellular Na(+) concentration in the halotolerant alga Dunaliella salina was measured in intact cells by (23)Na-NMR spectroscopy, utilizing the dysprosium tripolyphosphate complex as a sodium shift reagent, and was found to be 88 +/- 28 millimolar. Intracellular sodium ion content and intracellular volume were the same, within the experimental error, in cells adapted to grow in media containing between 0.1 and 4.0 molar NaCl. These values assume extracellular and intracellular NMR visibilities of the (23)Na nuclei of 100 and 40%, respectively. The relaxation rate of intracellular sodium was enhanced with increasing salinity of the growth medium, in parallel to the intracellular osmosity due to the presence of glycerol, indicating that Na(+) ions and glycerol are codistribbuted within the cell volume.

    View details for Web of Science ID A1988P690800008

    View details for PubMedID 16666230

  • P-31 AND C-13-NMR STUDIES OF THE PHOSPHORUS AND CARBON METABOLITES IN THE HALOTOLERANT ALGA, DUNALIELLA-SALINA PLANT PHYSIOLOGY BENTAL, M., ORENSHAMIR, M., AVRON, M., Degani, H. 1988; 87 (2): 320-324

    Abstract

    The intracellular phosphorus and carbon metabolites in the halotolerant alga Dunaliella salina adapted to different salinities were monitored in living cells by (31)P- and (13)C-nuclear magnetic resonance (NMR) spectroscopy. The (13)C-NMR studies showed that the composition of the visible intracellular carbon metabolites other than glycerol is not significantly affected by the salinity of the growth medium. The T(1) relaxation rates of the (13)C-glycerol signals in intact cells were enhanced with increasing salinity of the growth medium, in parallel to the expected increase in the intracellular viscosity due to the increase in intracellular glycerol. The (31)P-NMR studies showed that cells adapted to the various salinities contained inorganic phosphate, phosphomonoesters, high energy phosphate compounds, and long chain polyphosphates. In addition, cells grown in media containing up to 1 molar NaCl contained tripolyphosphates. The tripolyphosphate content was also controlled by the availability of inorganic phosphate during cell growth. Phosphate-depleted D. salina contained no detectable tripolyphosphate signal. Excess phosphate, however, did not result in the appearance of tripolyphosphate in (31)P-NMR spectra of cells adapted to high (>1.5 molar NaCl) salinites.

    View details for Web of Science ID A1988N897900007

    View details for PubMedID 16666141

  • CA-2+-INDUCED FUSION OF LARGE UNILAMELLAR PHOSPHATIDYLSERINE CHOLESTEROL VESICLES BIOCHIMICA ET BIOPHYSICA ACTA BENTAL, M., Wilschut, J., Scholma, J., Nir, S. 1987; 898 (2): 239-247

    Abstract

    The effect of cholesterol on the Ca2+-induced aggregation and fusion of large unilamellar phosphatidylserine (PS) vesicles has been investigated. Mixing of aqueous vesicle contents was followed continuously with the Tb/dipicolinate assay, while the dissociation of pre-encapsulated Tb/dipicolinate complex was taken as a measure of the release of vesicle contents. Vesicles consisting of pure PS or PS/cholesterol mixtures at molar ratios of 4:1, 2:1 and 1:1 were employed at three different lipid concentrations, each at four different Ca2+ concentrations. The results could be well simulated in terms of a mass-action kinetic model, providing separately the rate constants of vesicle aggregation, c11, and of the fusion reaction itself, f11. In the analyses the possibility of deaggregation of aggregated vesicles was considered explicitly. Values of both c11 and f11 increase steeply with the Ca2+ concentration increasing from 2 to 5 mM. With increasing cholesterol content of the vesicles the value of c11 decreases, while the rate of the actual fusion reaction, f11, increases. Remarkably, the effect of cholesterol on both aggregation and fusion is quite moderate. The presence of cholesterol in the vesicle bilayer does not affect the leakage of vesicle contents during fusion.

    View details for Web of Science ID A1987H022500016

    View details for PubMedID 3828344

  • PROMOTION AND INHIBITION OF VESICLE FUSION BY POLYLYSINE BIOCHEMISTRY Gad, A. E., BENTAL, M., ELYASHIV, G., Weinberg, H., Nir, S. 1985; 24 (22): 6277-6282

    Abstract

    Polylysine induced rapid aggregation of large unilamellar vesicles composed of phosphatidylcholine-cardiolipin (1:1 molar ratio) but not their fusion. Application of the terbium-dipicolinic acid fusion assay showed that addition of polylysine at nanomolar concentrations enabled a significant lowering of the Ca2+ threshold concentration for vesicle fusion from 9 to 1 mM. Analysis of the kinetics of fusion with a mass-action kinetic model showed that polylysine enhanced significantly the rate of aggregation but affected only slightly the rate of fusion per se. Maximal enhancement of overall fusion rates occurred at a charge ratio (polylysine/cardiolipin) of about 0.5. At larger polylysine concentrations, e.g., at charge ratios greater than 3, polylysine inhibited vesicle fusion.

    View details for Web of Science ID A1985ATX1400035

    View details for PubMedID 4084519

  • CA-2+-INDUCED FUSION OF PHOSPHATIDYLSERINE VESICLES - MASS-ACTION KINETIC-ANALYSIS OF MEMBRANE LIPID MIXING AND AQUEOUS CONTENTS MIXING BIOCHIMICA ET BIOPHYSICA ACTA Wilschut, J., Scholma, J., BENTAL, M., Hoekstra, D., Nir, S. 1985; 821 (1): 45-55

    Abstract

    We have investigated the initial kinetics of Ca2+-induced aggregation and fusion of phosphatidylserine large unilamellar vesicles at 3, 5 and 10 mM Ca2+ and 15, 25 and 35 degrees C, utilizing the Tb/dipicolinate (Tb/DPA) assay for mixing of aqueous vesicle contents and a resonance energy transfer (RET) assay for mixing of bilayer lipids. Separate rate constants for vesicle aggregation as well as deaggregation and for the fusion reaction itself were determined by analysis of the data in terms of a mass action kinetic model. At 15 degrees C the aggregation rate constants for either assay are the same, indicating that at this temperature all vesicle aggregation events that result in lipid mixing lead to mixing of aqueous contents as well. By contrast, at 35 degrees C the RET aggregation rate constants are higher than the Tb/DPA aggregation rate constants, indicating a significant frequency of reversible vesicle aggregation events that do result in mixing of bilayer lipids, but not in mixing of aqueous vesicle contents. In any conditions, the RET fusion rate constants are considerably higher than the Tb/DPA fusion rate constants, demonstrating the higher tendency of the vesicles, once aggregated, to mix lipids than to mix aqueous contents. This possibly reflects the formation of an intermediate fusion structure. With increasing Ca2+ concentrations the RET and the Tb/DPA fusion rate constants increase in parallel with the respective aggregation rate constants. This suggests that fusion susceptibility is conferred on the vesicles during the process of vesicle aggregation and not solely as a result of the interaction of Ca2+ with isolated vesicles. Aggregation of the vesicles in the presence of Mg2+ produces neither mixing of aqueous vesicle contents nor mixing of bilayer lipids.

    View details for Web of Science ID A1985AVE4300006

    View details for PubMedID 4063361

  • CA-2+-INDEPENDENT, PROTEIN-MEDIATED FUSION OF CHROMAFFIN GRANULE GHOSTS WITH LIPOSOMES BIOCHIMICA ET BIOPHYSICA ACTA BENTAL, M., Lelkes, P. I., Scholma, J., Hoekstra, D., Wilschut, J. 1984; 774 (2): 296-300

    Abstract

    We have investigated the interaction between isolated membrane vesicles from chromaffin granules and large unilamellar phospholipid vesicles (liposomes). Mixing of membrane lipids has been monitored continuously, utilizing the fluorescence resonance energy transfer assay described by Struck et al. ((1982) Biochemistry 20, 4093-4099). To demonstrate coalescence of the internal vesicle volumes the transfer of colloidal gold from the liposomes to the interior of the granule membrane vesicles has been examined. Efficient fusion of the liposomes with the granule membranes was observed. Significant fusion occurred in the absence of Ca2+, although the extent of interaction was enhanced in its presence. The sensitivity of the interaction to pretreatment of the granule membranes with trypsin showed the fusion reaction to be a protein-mediated process.

    View details for Web of Science ID A1984TD63200019

    View details for PubMedID 6331508