Shashwati Basak
Biocon Bristol-Myers Squibb Research and Development Center, Indiahttps://www.facebook.com/shasho001
Title: Clinical biomarkers in drug development: Quantitative PCR-Based fit-for-purpose assay qualification
Friday, 6 May 2016
MAYLAND CHANG
MAYLAND CHANG
Research Professor at University of Notre Dame
https://www.linkedin.com/in/mayland-chang-97b1b432
........
MAYLAND CHANG
- Research Professor; Director, Chemistry-Biochemistry-Biology Interface (CBBI) Program
- Office: 247 NSH
- Phone: (574) 631-2965
Dr. Chang obtained B.S. degrees in
biological sciences and chemistry from the University of Southern
California, and a Ph.D. in chemistry from the University of Chicago.
Subsequently, she conducted postdoctoral research at Columbia University
as a National Institutes of Health postdoctoral fellow. She joined the
faculty of the University of Notre Dame in 2003. Previously, Dr. Chang
was Chief Operating Officer of University Research Network,
Inc., Senior Scientist with Pharmacia Corporation, and Senior Chemist at
Dow Chemical Company. She has characterized the ADME properties
of numerous drugs, as well as prepared NDAs, INDs, Investigator’s
Brochures, product development plans, and candidate drug evaluations.
The Chang lab conducts biomedical research to understand the molecular basis of disease and to design small molecules for therapeutic intervention. Some of our current projects are:
SB-3CT is a selective gelatinase (MMP-2 and MMP-9) inhibitor that shows efficacy in animal models of stroke, traumatic brain injury, and cancer metastasis. SB-3CT, however, is poorly water soluble and is extensively metabolized. We used a prodrug strategy to increase >5000-fold the aqueous solubility of SB-3CT. The prodrugs are hydrolyzed in human blood within 30 minutes, generating the active gelatinase inhibitors. One of the prodrugs (referred to as ND-478) has excellent pharmacokinetic properties. This class of compounds is rapidly absorbed andis readily distributed to the brain. Efficacy studies in animal models of stroke and traumatic brain injury are currently being conducted.
Chronic wounds are a complication of diabetes and are characterized by inflammation, altered MMP expression, and deregulation of apoptosis. We used an affinity resin that binds only the active forms of MMPs and related ADAMs coupled with quantitative proteomics to identify active MMPs in diabetic wounds. Using the selective MMP-9 inhibitor ND-322 led to acceleration of wound healing accompanied by re-epithelialization. This represents the first pharmacological intervention in treatment of diabetic wounds. Studies to confirm the roles of these MMPs in diabetic wound healing are underway.
Another project involves the design, syntheses, and evaluation of novel antibiotics to treat methicillin-resistant Staphylococcus aureus infections. We have identified two lead templates that show high in vitro activity and promising antibacterial activity in a mouse model of infection. Their pharmacokinetic properties are being optimized. Identification of the target is being pursued by photoaffinity labeling at the whole proteome level, as well as obtaining an X-ray crystal structure of the compounds with the putative target.
Research Professor, Chemistry & Biochemistry
University of Notre Dame
Email: Mayland Chang
Phone: 574-631-6533
Office: 163 Stepan Hall
Mayland Chang, Department of Chemistry and Biochemistry, is working on ways to inhibit cancer metastasis, the spreading of the out-of-control cells to other organs. Although metastasis is a leading reason that cancer becomes fatal, primary tumors rarely kill and often can be treated, no anti-metastatic agent has been commercialized to treat aggressive cancers. Meanwhile, metastasis of breast and prostate cancer, for example, leads to further life-threatening complications that cause tens of thousands of deaths each year.
Building on studies showing that the matrix metal-loproteinases are associated with cancer progression and metastasis in many types of cancers, a few years ago discovered and
synthesized the first prototype selective mechanism-based inhibitor found to be effective in mouse models of prostate cancer metastasis to the bone, breast cancer metastasis to the lungs, and T-cell lymphoma metastasis to the liver. This work has progressed in the direction of compounds that can be used in additional in vivo models for disease, leading to second and third-generation compounds. The researchers are now refining related compounds with the goal of developing selective inhibitors that can advance forward to preclinical development and ultimate entry into clinical trials for the treatment of cancer metastasis.
Mayland
Chang, PhD, is bringing scientific discoveries out of academia to the
masses, from new antibiotics to the treatment of skull-crunching head
injuries on the football field.
Chang, a faculty member in the Department of Chemistry and Biochemistry, was recently awarded a five year, $5.5 million dollar grant from the National Institute of Allergy and Infectious Diseases (NIAID). She is also the recent recipient of an NFL Charities grant to design and develop therapeutics for the treatment of traumatic brain injury (TBI).
The NIAID grant, a considerably large amount for research grants, will fund translational research aimed at the discovery and development of drugs to fight serious gram-positive bacterial infections such as methicillian resistant Staphylococcus aureus (MRSA). Translational research is described by Chang as “bench to bedside” research, which leads to practical applications in patients.
Chang obtained B.S. degrees in biological sciences and chemistry from the University of Southern California, and a Ph.D. in chemistry from the University of Chicago. She joined Notre Dame in 2003.
Chang recently spoke with ND Today about her research, teaching at Notre Dame, and her hobbies.
ND Today: What does it mean to you to receive the NIAID grant?
Mayland Chang: There is a dearth of research on new antibacterials, as the economic incentives are not there for pharmaceutical companies to pursue discovery and development of antibiotics. Because fewer pharmaceutical companies are focusing on antibacterials (most have abandoned the field), academic institutions have to step up to discover and develop new classes of antibiotics. This grant allows us to do just that.
ND Today: Tell us about your NFL Charities Grant – what type of research will you be doing?
MC: Traumatic brain injury (TBI) is one of the leading causes of death and disability in the industrialized world. A TBI is caused by a bump, blow, or jolt to the head or a penetrating head injury that disrupts the normal function of the brain. The majority of TBIs (75%) are concussions. Concussions are a prominent feature of sports, with 300,000 reported concussions in the U.S. occurring while playing sports. Concussions result from a blow to the head that produces a cascade of neurological events, resulting in reduced blood flow to the brain, brain cell injury, and death.
A contributing factor to these pathological processes is the activation of enzymes called matrix metalloproteinases (MMPs), particularly gelatinases (MMP-2 and MMP-9). There are presently no therapeutics for TBI. Research in the field lacks presently the ability to rescue brain cells after each concussion or any damage to the brain. If a medication could be given after such a damage that rescues the brain cells destined to die that would move the field forward in treatment of TBI significantly. The NFL Charities grant will support groundbreaking research that has the potential for the development of such a treatment for TBI. We have developed a prototype inhibitor, which potently decreases brain damage and hemorrhagic injury. We have synthesized water-soluble inhibitors, which are amenable to intravenous administration, the preferred route of administration for TBI. These results hold outstanding promise for important applications in fighting gelatinase-mediated consequences of brain damage after TBI in patients.NFL funding will open the door for expansion of this project in directions that we hope will lead to treatments for TBI.
ND Today: How did you come to specialize in chemistry?
MC: I grew up in Ecuador and was good in math and science. As a high school student, I only knew of professional careers, such as medicine. I came to the US for college and as an undergraduate at USC I started as a biology major. There was no pre-med major at USC. After taking analytical chemistry as a junior in college, I decided to pursue chemistry. I ended up with a BS in biology and a BS in chemistry. Then I went to graduate school at the University of Chicago and got my PhD as a natural products chemist and post-doc at Columbia University in bioanalytical chemistry. When I was looking for a job, I could not find a position in the industry in natural products chemistry. I ended up doing metabolism of herbicides and insecticides at Dow Chemical. From there I moved to Upjohn. Before moving to Notre Dame, I was COO of University Research Network, Inc., an academic research organization that I established for Wayne State University School of Medicine that facilitated clinical research and provided clinical development services to the pharmaceutical and biotechnology industries.
ND Today: What is the best part about working at Notre Dame?
MC: The opportunity to work with and train talented undergraduate students. Since I came to Notre Dame, I have had nine undergraduates in the lab—four have graduated, one is in grad school at Madison Wisconsin, one is in an MD PhD program at Washington University, one is in an MD program at Loyola, and one is in an MD program at Rochester.
ND Today: Given the very serious nature of your work, what do you like to do to unwind?
MC: Gourmet cooking. Cooking is very much like chemistry. I wanted to be a chef but it was not an acceptable profession [in her home country]. Gardening—pulling weeds relieves stress, and travel—traveling is part of one’s education—it opens the mind to new experiences and cultures. I love to spend time with my cats Misty and Carbon, and watching birds in my backyard. Rain or shine, I feed the birds year-round.
Mayland Chang
Diabetes affects more than 29 million Americans, or 9.3 percent of
the population. One of the many complications of the disease is the
inability of wounds to heal properly because diabetic patients often
have nerve damage, weakened immune systems or narrow arteries. In 2010,
73,000 non-traumatic lower-limb amputations were performed in the United
States due to diabetes.
The American Diabetes Association (ADA) announced Tuesday that it is funding a $1.6 million Accelerator Award to Mayland Chang, research professor of chemistry and biochemistry at the University of Notre Dame, to help lower that number. The research award, part of the association’s Pathway Awards program, will provide funding for Chang’s project, “A Strategy to Accelerate Diabetic Wound Repair,” over five years.
Chang’s research is broadly focused on exploring the molecular basis of disease and designing small molecules for therapeutic interventions. She has ongoing projects related to stroke, traumatic brain injury, cancer metastasis and MRSA (methicillin-resistant Staphylococcus aureus). A newer area of work for Chang is to understand why diabetic wounds are so difficult to treat and to develop novel therapeutics to promote wound healing.
Using a mouse model and a novel diagnostic resin that binds to active forms of matrix metalloproteinases (MMPs), proteases involved in tissue remodeling, Chang’s research group found that MMP-9 may cause diabetic wounds and MMP-8 may be involved in wound repair. They also demonstrated that selective pharmacological inhibition of MMP-8 delayed wound repair and inhibition of MMP-9 accelerated wound healing.
Using a combination of research techniques, Chang’s project will identify the mechanisms associated with diabetic wound development, progression and healing; study bacterial colonization in diabetic wounds; and find interventions that expedite the healing process. To achieve these goals, she will validate the roles of MMP-8 and MMP-9 in diabetic wounds, investigate the relevance of these MMPs in human patients, evaluate novel MMP-9 inhibitors and determine the contribution of bacterial infection on wound repair.
“This research project will allow intervention of chronic wounds, a complication of diabetes for which pharmacological clinical recourse is not available,” Chang said. “Our work holds great promise in addressing an unmet medical need.”
Accelerator Awards are designed to support early-career investigators or established researchers who are accomplished in other fields, but would like to apply their expertise to innovative diabetes-related research topics.
Contact: Mayland Chang, 574-631-2965, mchang@nd.edu
////
- Research Professor; Director, Chemistry-Biochemistry-Biology Interface (CBBI) Program
- Office: 247 NSH
- Phone: (574) 631-2965
- Send an email
Primary Research Areas
Research Specialties
Experience
Director, CBBI Program
University of Notre Dame
Research Professor
University of Notre Dame
Senior Scientist
Pharmacia
Senior Chemist
Dow Chemical
Education
University of Chicago
Ph.D., Chemistry
The Chang lab conducts biomedical research to understand the molecular basis of disease and to design small molecules for therapeutic intervention. Some of our current projects are:
SB-3CT is a selective gelatinase (MMP-2 and MMP-9) inhibitor that shows efficacy in animal models of stroke, traumatic brain injury, and cancer metastasis. SB-3CT, however, is poorly water soluble and is extensively metabolized. We used a prodrug strategy to increase >5000-fold the aqueous solubility of SB-3CT. The prodrugs are hydrolyzed in human blood within 30 minutes, generating the active gelatinase inhibitors. One of the prodrugs (referred to as ND-478) has excellent pharmacokinetic properties. This class of compounds is rapidly absorbed andis readily distributed to the brain. Efficacy studies in animal models of stroke and traumatic brain injury are currently being conducted.
Chronic wounds are a complication of diabetes and are characterized by inflammation, altered MMP expression, and deregulation of apoptosis. We used an affinity resin that binds only the active forms of MMPs and related ADAMs coupled with quantitative proteomics to identify active MMPs in diabetic wounds. Using the selective MMP-9 inhibitor ND-322 led to acceleration of wound healing accompanied by re-epithelialization. This represents the first pharmacological intervention in treatment of diabetic wounds. Studies to confirm the roles of these MMPs in diabetic wound healing are underway.
Another project involves the design, syntheses, and evaluation of novel antibiotics to treat methicillin-resistant Staphylococcus aureus infections. We have identified two lead templates that show high in vitro activity and promising antibacterial activity in a mouse model of infection. Their pharmacokinetic properties are being optimized. Identification of the target is being pursued by photoaffinity labeling at the whole proteome level, as well as obtaining an X-ray crystal structure of the compounds with the putative target.
Recent Papers
-
Spink, E.; Ding, D.R.; Peng, Z.H.; Boudreau, M.A.; Leemans, E.;
Lastochkin, E.; Song, W.; Lichtenwalter, K.; O'Daniel, P.I.; Testero,
S.A.; Pi, H.L.; Schroeder, V.A.; Wolter, W.R.; Antunes, N.T.; Suckow,
M.A.; Vakulento, S.; Chang, M.; Mobashery, S. "Structure-Activity
Relationship for the Oxadiazole Class of Antibiotics." J. Med. Chem. 2015, 58 (3), 1380-1389.
-
Bouley, R.; Kumarasiri, M.; Peng, Z.H.; Otero, L.H.; Song, W.;
Suckow, M.A.; Schroeder, V.A.; Wolter, W.R.; Lastochkin, E.; Antunes,
N.T.; Pi, H.K.; Vakulento, S.; Hermoso, J.A.; Chang, M.; Mobashery, S.
"Discovery of Antibiotic
(E)-3-(3-Carboxyphenyl)-2-(4-cyanostyryl)quinazolin-4(3H)-one." J. Am. Chem. Soc. 2015, 137 (5), 1738-1741.
-
Ding, D.R.; Lichtenwalter, K.; Pi, H.L.; Mobashery, S.; Chang, M.
"Characterization of a selective inhibitor for matrix
metalloproteinase-8 (MMP-8)." MedChemComm 2014, 5 (9), 1381-1383.
-
O'Daniel, P.I.; Peng, Z.H.; Pi, H.L.; Testero, S.A.; Ding, D.R.;
Spink, E.; Leemans, E.; Boudreau, M.A.; Yamaguchi, T.; Schroeder, V.A.;
Wolter, W.R.; Llarrull, L.I.; Song, W.; Lastochkin, E.; Kumarasiri, M.;
Antunes, N.T.; Espahbodi, M.; Lichtenwalter, K.; Suckow, M.A.;
Vakulenko, S.; Mobashery, S.; Chang, M. "Discovery of a New Class of
Non-beta-lactam Inhibitors of Penicillin-Binding Proteins with
Gram-Positive Antibacterial Activity." J. Am. Chem. Soc. 2014, 136 (9), 3664-3672.
-
Gooyit, M.; Peng, Z.H.; Wolter, W.R.; Pi, H.L.; Ding, D.R.; Hesek,
D.; Lee, M.; Boggess, B.; Champion, M.M.; Suckow, M.A.; Mobashery, S.;
Chang, M. "A Chemical Biological Strategy to Facilitate Diabetic Wound
Healing." ACS Chem. Biol. 2014, 9 (1), 105-110.
-
Gooyit, M.; Song, W.; Mahasenan, K.V.; Lichtenwalter, K.; Suckow,
M.A.; Schroeder, V.A.; Wolter, W.R.; Mobashery, S.; Chang, M. "O-Phenyl
Carbamate and Phenyl Urea Thiiranes as Selective Matrix
Metalloproteinase-2 Inhibitors that Cross the Blood Brain Barrier." J. Med. Chem. 2013, 56 (20), 8139-8150.
Mike and Josie Harper Cancer Research Institute
Mayland Chang
Mayland ChangResearch Professor, Chemistry & Biochemistry
University of Notre Dame
Email: Mayland Chang
Phone: 574-631-6533
Office: 163 Stepan Hall
Mayland Chang, Department of Chemistry and Biochemistry, is working on ways to inhibit cancer metastasis, the spreading of the out-of-control cells to other organs. Although metastasis is a leading reason that cancer becomes fatal, primary tumors rarely kill and often can be treated, no anti-metastatic agent has been commercialized to treat aggressive cancers. Meanwhile, metastasis of breast and prostate cancer, for example, leads to further life-threatening complications that cause tens of thousands of deaths each year.
Building on studies showing that the matrix metal-loproteinases are associated with cancer progression and metastasis in many types of cancers, a few years ago discovered and
synthesized the first prototype selective mechanism-based inhibitor found to be effective in mouse models of prostate cancer metastasis to the bone, breast cancer metastasis to the lungs, and T-cell lymphoma metastasis to the liver. This work has progressed in the direction of compounds that can be used in additional in vivo models for disease, leading to second and third-generation compounds. The researchers are now refining related compounds with the goal of developing selective inhibitors that can advance forward to preclinical development and ultimate entry into clinical trials for the treatment of cancer metastasis.
Five Questions with Mayland Chang
Mayland
Chang, PhD, is bringing scientific discoveries out of academia to the
masses, from new antibiotics to the treatment of skull-crunching head
injuries on the football field. Chang, a faculty member in the Department of Chemistry and Biochemistry, was recently awarded a five year, $5.5 million dollar grant from the National Institute of Allergy and Infectious Diseases (NIAID). She is also the recent recipient of an NFL Charities grant to design and develop therapeutics for the treatment of traumatic brain injury (TBI).
The NIAID grant, a considerably large amount for research grants, will fund translational research aimed at the discovery and development of drugs to fight serious gram-positive bacterial infections such as methicillian resistant Staphylococcus aureus (MRSA). Translational research is described by Chang as “bench to bedside” research, which leads to practical applications in patients.
Chang obtained B.S. degrees in biological sciences and chemistry from the University of Southern California, and a Ph.D. in chemistry from the University of Chicago. She joined Notre Dame in 2003.
Chang recently spoke with ND Today about her research, teaching at Notre Dame, and her hobbies.
ND Today: What does it mean to you to receive the NIAID grant?
Mayland Chang: There is a dearth of research on new antibacterials, as the economic incentives are not there for pharmaceutical companies to pursue discovery and development of antibiotics. Because fewer pharmaceutical companies are focusing on antibacterials (most have abandoned the field), academic institutions have to step up to discover and develop new classes of antibiotics. This grant allows us to do just that.
ND Today: Tell us about your NFL Charities Grant – what type of research will you be doing?
MC: Traumatic brain injury (TBI) is one of the leading causes of death and disability in the industrialized world. A TBI is caused by a bump, blow, or jolt to the head or a penetrating head injury that disrupts the normal function of the brain. The majority of TBIs (75%) are concussions. Concussions are a prominent feature of sports, with 300,000 reported concussions in the U.S. occurring while playing sports. Concussions result from a blow to the head that produces a cascade of neurological events, resulting in reduced blood flow to the brain, brain cell injury, and death.
A contributing factor to these pathological processes is the activation of enzymes called matrix metalloproteinases (MMPs), particularly gelatinases (MMP-2 and MMP-9). There are presently no therapeutics for TBI. Research in the field lacks presently the ability to rescue brain cells after each concussion or any damage to the brain. If a medication could be given after such a damage that rescues the brain cells destined to die that would move the field forward in treatment of TBI significantly. The NFL Charities grant will support groundbreaking research that has the potential for the development of such a treatment for TBI. We have developed a prototype inhibitor, which potently decreases brain damage and hemorrhagic injury. We have synthesized water-soluble inhibitors, which are amenable to intravenous administration, the preferred route of administration for TBI. These results hold outstanding promise for important applications in fighting gelatinase-mediated consequences of brain damage after TBI in patients.NFL funding will open the door for expansion of this project in directions that we hope will lead to treatments for TBI.
ND Today: How did you come to specialize in chemistry?
MC: I grew up in Ecuador and was good in math and science. As a high school student, I only knew of professional careers, such as medicine. I came to the US for college and as an undergraduate at USC I started as a biology major. There was no pre-med major at USC. After taking analytical chemistry as a junior in college, I decided to pursue chemistry. I ended up with a BS in biology and a BS in chemistry. Then I went to graduate school at the University of Chicago and got my PhD as a natural products chemist and post-doc at Columbia University in bioanalytical chemistry. When I was looking for a job, I could not find a position in the industry in natural products chemistry. I ended up doing metabolism of herbicides and insecticides at Dow Chemical. From there I moved to Upjohn. Before moving to Notre Dame, I was COO of University Research Network, Inc., an academic research organization that I established for Wayne State University School of Medicine that facilitated clinical research and provided clinical development services to the pharmaceutical and biotechnology industries.
ND Today: What is the best part about working at Notre Dame?
MC: The opportunity to work with and train talented undergraduate students. Since I came to Notre Dame, I have had nine undergraduates in the lab—four have graduated, one is in grad school at Madison Wisconsin, one is in an MD PhD program at Washington University, one is in an MD program at Loyola, and one is in an MD program at Rochester.
ND Today: Given the very serious nature of your work, what do you like to do to unwind?
MC: Gourmet cooking. Cooking is very much like chemistry. I wanted to be a chef but it was not an acceptable profession [in her home country]. Gardening—pulling weeds relieves stress, and travel—traveling is part of one’s education—it opens the mind to new experiences and cultures. I love to spend time with my cats Misty and Carbon, and watching birds in my backyard. Rain or shine, I feed the birds year-round.
Mayland Chang receives $1.6M American Diabetes Association research award
Mayland ChangThe American Diabetes Association (ADA) announced Tuesday that it is funding a $1.6 million Accelerator Award to Mayland Chang, research professor of chemistry and biochemistry at the University of Notre Dame, to help lower that number. The research award, part of the association’s Pathway Awards program, will provide funding for Chang’s project, “A Strategy to Accelerate Diabetic Wound Repair,” over five years.
Chang’s research is broadly focused on exploring the molecular basis of disease and designing small molecules for therapeutic interventions. She has ongoing projects related to stroke, traumatic brain injury, cancer metastasis and MRSA (methicillin-resistant Staphylococcus aureus). A newer area of work for Chang is to understand why diabetic wounds are so difficult to treat and to develop novel therapeutics to promote wound healing.
Using a mouse model and a novel diagnostic resin that binds to active forms of matrix metalloproteinases (MMPs), proteases involved in tissue remodeling, Chang’s research group found that MMP-9 may cause diabetic wounds and MMP-8 may be involved in wound repair. They also demonstrated that selective pharmacological inhibition of MMP-8 delayed wound repair and inhibition of MMP-9 accelerated wound healing.
Using a combination of research techniques, Chang’s project will identify the mechanisms associated with diabetic wound development, progression and healing; study bacterial colonization in diabetic wounds; and find interventions that expedite the healing process. To achieve these goals, she will validate the roles of MMP-8 and MMP-9 in diabetic wounds, investigate the relevance of these MMPs in human patients, evaluate novel MMP-9 inhibitors and determine the contribution of bacterial infection on wound repair.
“This research project will allow intervention of chronic wounds, a complication of diabetes for which pharmacological clinical recourse is not available,” Chang said. “Our work holds great promise in addressing an unmet medical need.”
Accelerator Awards are designed to support early-career investigators or established researchers who are accomplished in other fields, but would like to apply their expertise to innovative diabetes-related research topics.
Contact: Mayland Chang, 574-631-2965, mchang@nd.edu
Renee Bouley
Renee Bouley
'
LINKS
Summary
I
am an interdisciplinary PhD candidate that headed an antibiotic
discovery project resulting in a patent application and 1 first-author
publication in Journal of the American Chemical Society. I have been
trained in organic chemistry, microbiology, biochemistry, pharmacology,
and x-ray crystallography and co-authored 4 publications including 1
publication in Nature Chemical Biology. Additionally, I have been
awarded 2 individual fellowships during my graduate career from the
American Chemical Society and National Institutes of Health.
Conference Poster 2014
Resume 2015
Nature Chemical Biology cover November 2015
Education
University of Notre Dame
PhD, Organic Chemistry
1 first-author publication, 3 contributing author publications, 1 contributing author on patent application
Activities and Societies: Chemistry-Biology-Biochemistry Interface Steering Committee Student Representative, American Association for the Advancement of Science (AAAS) Member, American Chemical Society (ACS) Member
- (Open)5 honors and awards
Grand Valley State University
Bachelors of Science, Chemistry
1 first author publication
- (Open)1 honor or award
Experience
Graduate Student
University of Notre Dame
Synthesized 40 analogs and determined a structure-activity relationship.
Determined metabolic stability and plasma stability of synthetic compounds
Evaluated synthetic compounds in mouse models of infection
Identified the biological target and mechanism of action of synthetic compounds by protein activity assays, protein-ligand crystal complexes, and macromolecular synthesis assays
Determined metabolic stability and plasma stability of synthetic compounds
Evaluated synthetic compounds in mouse models of infection
Identified the biological target and mechanism of action of synthetic compounds by protein activity assays, protein-ligand crystal complexes, and macromolecular synthesis assays
- (Open)1 honor or award
Research Internship
Consejo Superior de Investigaciones CientÃficas
Grew crystals of membrane protein and performed co-crystallization studies with ligands
Measured protein crystals at the Swiss Light Source in Zurich, Switzerland
Analyzed the diffraction data by molecular replacement
Measured protein crystals at the Swiss Light Source in Zurich, Switzerland
Analyzed the diffraction data by molecular replacement
Teaching Assistant
University of Notre Dame
Fall 2010:
Supervised and instructed students majoring in chemistry in organic chemistry techniques
Graded weekly lab reports and course exams
Spring 2011 & Fall 2011:
Led weekly discussion sections in which students worked on problem sets
Gave short lectures on the background information needed to complete each problem set
Graded weekly problem sets and course exams
Supervised and instructed students majoring in chemistry in organic chemistry techniques
Graded weekly lab reports and course exams
Spring 2011 & Fall 2011:
Led weekly discussion sections in which students worked on problem sets
Gave short lectures on the background information needed to complete each problem set
Graded weekly problem sets and course exams
Student Learning Assistance Facilitator
Grand Valley State University
Led weekly discussions in which students worked on problems sets I prepared
Gave lectures that reviewed relevant course material
Gave lectures that reviewed relevant course material
Chemistry Tutor
Grand Valley State University
Met
with individual students and small groups (up to 4) of students on a
weekly basis to provide help with homework or material they found
difficult to understand.
Research Assistant
Grand Valley State University
Synthesized a polyaniline matrix and incorporated onto electrodes
Measured polyaniline matrices by electrochemical impedance spectroscopy (EIS)
Measured resistance and capacitance of a redox protein, cytochrome c, by EIS
Measured polyaniline matrices by electrochemical impedance spectroscopy (EIS)
Measured resistance and capacitance of a redox protein, cytochrome c, by EIS
Analytical Chemistry Intern
Alticor
Evaluated anti-inflammatory activity of botanical extracts using a MMP-9 protein activity assay
Evaluated botanical extracts for effects on melanonin production using a mouse tryosinase protein activity assay
Quantified solubility of active ingredients in botanical extracts using HPLC
Evaluated botanical extracts for effects on melanonin production using a mouse tryosinase protein activity assay
Quantified solubility of active ingredients in botanical extracts using HPLC
Honors & Awards
Baxter Young Investigator Award
Baxter Healthcare
Second Tier Awardee for Baxter Young Investigator Award
http://www.baxter.com/inside-baxter/science/programs/young-investigator-award.page
http://www.baxter.com/inside-baxter/science/programs/young-investigator-award.page
Ruth L. Kirschstein NRSA Individual Predoctoral Fellowship (F31)
National Institute of Allergy and Infectious Disease
http://science.nd.edu/news/55138-renee-bouley-earns-kirschstein-national-research-service-award-from-nih/
http://grants.nih.gov/grants/guide/pa-files/PA-14-147.html
http://grants.nih.gov/grants/guide/pa-files/PA-14-147.html
American Chemical Society Division of Medicinal Chemistry Predoctoral Fellowship
American Chemical Society Division of Medicinal Chemistry
http://science.nd.edu/news/40973-renee-bouley-selected-to-receive-prestigious-acs-predoctoral-fellowship/
Chemistry-Biochemistry-Biology Interface Fellowship
University of Notre Dame
Program
at Notre Dame funded by the NIH to provide training to students at the
interface of chemistry and the biological sciences.
Chemistry-Biology-Biochemistry Interface Symposium Oral Presentation Competition Winner
University of Notre Dame
Chemistry-Biology-Biochemistry Interface Symposium Poster Competition Winner
University of Notre Dame
Undergraduate Award in Inorganic Chemistry
Grand Valley State University
Publications
Discovery of Antibiotic (E)-3-(3-Carboxyphenyl)-2-(4-cyanostyryl)quinazolin-4(3H)-one(Link)
Journal of the American Chemical Society
January 28, 2015
Highlighted in ACS Chem. Biol. 2015, 10, 639
Recommended by Faculty of 1000
Recommended by Faculty of 1000
Synergistic, collaterally-sensitive β-lactam combinations suppress resistance in MRSA.(Link)
Nature Chemical Biology
September 14, 2015
Methicillin-resistant
Staphylococcus aureus (MRSA) is one of the most prevalent
multidrug-resistant pathogens worldwide, exhibiting increasing
resistance to the latest antibiotic therapies. Here we show that the
triple β-lactam combination meropenem-piperacillin-tazobactam (ME/PI/TZ)
acts synergistically and is bactericidal against MRSA subspecies N315
and 72 other clinical MRSA isolates in vitro...more
Synthesis and Evaluation of 1,2,4-Triazolo[1,5-a]pyrimidines as Antibacterial Agents Against Enterococcus faecium(Link)
Journal of Medicinal Chemistry
April 29, 2015Exploration of Mild Copper-Mediated Coupling of Organotrifluoroborates in the Synthesis of Thiirane-Based Inhibitors of Matrixmetalloproteinases(Link)
Bioorganic and Medicinal Chemistry Letters
December 12, 2010Electrochemical Protein Redox Activity under Extreme Martian Conditions(Link)
Electrochemistry Society Transactions
May 29, 2009Renee Bouley selected to receive prestigious ACS Predoctoral Fellowship
This award supports doctoral candidates working in the area of medicinal chemistry who have demonstrated superior achievements as graduate students and who show potential for future work as independent investigators. These fellowships have been awarded annually since 1991 and include one year stipend support and an invitation to present the fellow’s research results at a special awards session at the ACS National Meeting.
Bouley’s work, conducted under the advisement of Shahriar Mobashery, Navari Family Professor in Life Sciences, and Mayland Chang, Research Professor and Director of the Chemistry-Biochemistry-Biology Interface (CBBI) Program, centers around the discovery of a new class of antibiotics that are selective against staphylococcal species of bacteria, including hard-to-treat methicillin-resistant Staphylococcus aureus (MRSA). She has already identified a class of compounds that has in vitro activity against bacteria and demonstrated efficacy in mice. Bouley spent three months in 2012 in the laboratory of Prof. Juan Hermoso at Consejo Superior de Investigaciones Cientificas in Madrid, Spain, where she solved the crystal structure of the lead compound in complex with its target protein. Her studies have shown an unprecedented mechanism of action that opens opportunities for clinical resurrection of β-lactam antibiotics in combination with the new antibiotics. Bouley’s work during her fellowship tenure will explore structural analogs of these compounds with the goal of optimizing their potency in vivo and improving their drug-like properties.
Bouley is already the recipient of a National Institutes of Health Ruth L. Kirschstein National Research Service Award – CBBI (Chemistry-Biochemistry-Biology Interface) Program, a CBBI Research Internship Award, and an American Heart Association Predoctoral Fellowship (declined)………..https://www.linkedin.com/in/renee-bouley-43243215
.Research experience
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Karuna Wankhede-Bhokare
.Dr. Karuna Wankhede-Bhokare
Postdoctoral Researcher, LMU
- Postdoctoral Researcher at Ludwig Maximilian University of Munich
Studied at University of MumbaiPast: Institute Of Science, Mumbai and B.N.Bandodkaer
Summary
With vast industrial research experience, looking for research scientist position where innovative ideas can be transformed into realities with continuous process of learning and sharing new skills.
Experience
Research Scientist
Wockhardt Research Centre
• Synthesis of New Chemical entities particularly antibiotics, β-lactam inhibitor molecules based upon SAR.
• Proposing and designing synthetic route for newer molecule and its synthesis with more than 90% HPLC.
• One of the major work includes synthesis and method development of WCK 5178 one of the lead molecule. During the development of this molecules developed coupling of Na-DBO core with hydrazide in water, which is the key step in the synthesis. Synthesis of all known impurities of WCK 5178.
• Synthesis and scale up of DBO core, one of the most important key intermediate for WCK 5178 by patentable route
• Identification of unknown and major impurity based upon NMR, formed during the synthesis of side chain of WCK 5178 at plant scale.
• Proposed and attempted synthesis of side chain of another promising lead molecule WCK 5153.
• Proposing and designing synthetic route for newer molecule and its synthesis with more than 90% HPLC.
• One of the major work includes synthesis and method development of WCK 5178 one of the lead molecule. During the development of this molecules developed coupling of Na-DBO core with hydrazide in water, which is the key step in the synthesis. Synthesis of all known impurities of WCK 5178.
• Synthesis and scale up of DBO core, one of the most important key intermediate for WCK 5178 by patentable route
• Identification of unknown and major impurity based upon NMR, formed during the synthesis of side chain of WCK 5178 at plant scale.
• Proposed and attempted synthesis of side chain of another promising lead molecule WCK 5153.
Research Scientist
Piraml Healthcare Ltd
• Synthesis of drug intermediates.
• Designing different synthetic routes, doing literature search and its screening using
various reagents and conditions and selecting cost effective and patentable route.
• Optimization of cost effective synthetic route, documenting results.
• Worked on synthesis intermediate of an anti-HIV molecule Amprenavir and Atazanavir, intermediate for Moxifloxacin, Donepezil drug molecule.
• Handling of small scale (0.1g-0.5g) to large scale (100g-500g) experiments.
• Designing different synthetic routes, doing literature search and its screening using
various reagents and conditions and selecting cost effective and patentable route.
• Optimization of cost effective synthetic route, documenting results.
• Worked on synthesis intermediate of an anti-HIV molecule Amprenavir and Atazanavir, intermediate for Moxifloxacin, Donepezil drug molecule.
• Handling of small scale (0.1g-0.5g) to large scale (100g-500g) experiments.
Education
University of Mumbai
PhD, Organic Chemistry
Worked on “Some Studies on [3+2] Cycloadducts” which includes:
• 1,3-Dipolar reactions of nitrile oxide with alkene and alkynes, click chemistry of azides and alkynes.
• The studies includes synthesis of few known and unknown 1,3-dipoles particularly nitrile oxides and azides.
• Employed these dipoles and dipolarophiles in cycloaddition study and to establish regio- and stereochemistry of the newly formed cycloadducts by spectral and chemical correlation.
• Applications of 1,3-dipolar cycloaddition reactions as a tool for the synthesis of bioconjugates particularly steroid and carbohydrate based conjugates.
• 1,3-Dipolar reactions of nitrile oxide with alkene and alkynes, click chemistry of azides and alkynes.
• The studies includes synthesis of few known and unknown 1,3-dipoles particularly nitrile oxides and azides.
• Employed these dipoles and dipolarophiles in cycloaddition study and to establish regio- and stereochemistry of the newly formed cycloadducts by spectral and chemical correlation.
• Applications of 1,3-dipolar cycloaddition reactions as a tool for the synthesis of bioconjugates particularly steroid and carbohydrate based conjugates.
Patents
A process for preparation of sodium salt of (2S, 5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane
India
Filed
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