2015 in Review: Top 10 Medical Research Articles

Medical scientists around the world perform wide-ranging research at improving human health and reducing the burden of diseases. The Michelson Medical Research Foundation staff is proud to highlight top 10 medical research articles of 2015.

2015 in Review #1: Antibiotic Resistance

A new antibiotic kills pathogens without detectable resistance

Journal: Nature • Authors: Losee L. Ling and Colleagues • Institutions: U.S.A. : NovoBiotic Pharmaceuticals; Cambridge, MA. Antimicrobial Discovery Center, Department of Biology; Northeastern University, Boston, MA. Germany : Institute of Medical Microbiology, Institute for Pharmaceutical Biology; University of Bonn, Germany. German Centre for Infection Research; DZIF. United Kingdom : Selcia; Ongar, Essex.

2015 in Review #1: Antibiotic Resistance

A new antibiotic kills pathogens without detectable resistance

Journal: Nature • Authors: Losee L. Ling and Colleagues • Institutions: U.S.A. : NovoBiotic Pharmaceuticals; Cambridge, MA. Antimicrobial Discovery Center, Department of Biology; Northeastern University, Boston, MA. Germany : Institute of Medical Microbiology, Institute for Pharmaceutical Biology; University of Bonn, Germany. German Centre for Infection Research; DZIF. United Kingdom : Selcia; Ongar, Essex.

2015 in Review #1: Antibiotic Resistance

A new antibiotic kills pathogens without detectable resistance
Journal: Nature • Authors: Losee L. Ling and Colleagues • Institutions: U.S.A. : NovoBiotic Pharmaceuticals; Cambridge, MA. Antimicrobial Discovery Center, Department of Biology; Northeastern University, Boston, MA. Germany : Institute of Medical Microbiology, Institute for Pharmaceutical Biology; University of Bonn, Germany. German Centre for Infection Research; DZIF. United Kingdom : Selcia; Ongar, Essex.

2015 in Review #1: Antibiotic Resistance

A new antibiotic kills pathogens without detectable resistance
Journal: Nature • Authors: Losee L. Ling and Colleagues • Institutions: U.S.A. : NovoBiotic Pharmaceuticals; Cambridge, MA. Antimicrobial Discovery Center, Department of Biology; Northeastern University, Boston, MA. Germany : Institute of Medical Microbiology, Institute for Pharmaceutical Biology; University of Bonn, Germany. German Centre for Infection Research; DZIF. United Kingdom : Selcia; Ongar, Essex.

The discovery of antibiotics transformed medicine and continues to save millions of lives each year. However, as antibiotic-resistant bacteria increase, effective antibiotic options become increasingly limited. Dr. Ling et al (2015) published a timely article in Nature, describing their research which focuses on the development of an experimental platform to grow previously unculturable bacteria. Antimicrobial activities by said bacteria were screened and the team discovered a new antibiotic, teixobactin, produced by Eleftheria terrae (1). In follow-up experiments teixobacin inhibits bacterial cell wall synthesis, and exhibits antimicrobial activities in response to all mutants of gram-positive bacteria Staphylococcus aureus and Mycobacterium tuberculosis. The process of discovering teixobacin offers a platform to search for new antibiotics to combat ever increasing antibiotic-resistant bacteria.

  1. A New Antibiotic Kills Pathogens Without Detectable Resistance [2015-01-22; Losee L. Ling, Tanja Schneider, Aaron J. Peoples, Amy L. Spoering, Ina Engels, Brian P. Conlon, Anna Mueller, Till F. Schäberle, Dallas E. Hughes, Slava Epstein, Michael Jones, Linos Lazarides, Victoria A. Steadman, Douglas R. Cohen, Cintia R. Felix, K. Ashley Fetterman, William P. Millett, Anthony G. Nitti, Ashley M. Zullo, Chao Chen & Kim Lewis, Nature. 2015 Jan 22;517(7535):455-9. doi: 10.1038/nature14098. Epub 2015 Jan 7.]
2015 in Review: #1 Antibiotic Resistance

A model of teixobactin targeting and resistance. The teixobactin producer is a Gram-negative bacterium protected from this compound by exporting it across the outer membrane permeability barrier (upper panel). In target Gram-positive organisms lacking an outer membrane, the targets are readily accessible on the outside where teixobactin binds precursors of peptidoglycan (PG) and WTA. CM, cytoplasmic membrane; CW, cell wall; OM, outer membrane; T, teixobactin. (Credit: Nature. 2015. 517:455-459).

2015 in Review: #1 Antibiotic Resistance

A model of teixobactin targeting and resistance. The teixobactin producer is a Gram-negative bacterium protected from this compound by exporting it across the outer membrane permeability barrier (upper panel). In target Gram-positive organisms lacking an outer membrane, the targets are readily accessible on the outside where teixobactin binds precursors of peptidoglycan (PG) and WTA. CM, cytoplasmic membrane; CW, cell wall; OM, outer membrane; T, teixobactin. (Credit: Nature. 2015. 517:455-459).

2015 in Review: #1 Antibiotic Resistance

A model of teixobactin targeting and resistance. The teixobactin producer is a Gram-negative bacterium protected from this compound by exporting it across the outer membrane permeability barrier (upper panel). In target Gram-positive organisms lacking an outer membrane, the targets are readily accessible on the outside where teixobactin binds precursors of peptidoglycan (PG) and WTA. CM, cytoplasmic membrane; CW, cell wall; OM, outer membrane; T, teixobactin. (Credit: Nature. 2015. 517:455-459).

2015 in Review: #1 Antibiotic Resistance

A model of teixobactin targeting and resistance. The teixobactin producer is a Gram-negative bacterium protected from this compound by exporting it across the outer membrane permeability barrier (upper panel). In target Gram-positive organisms lacking an outer membrane, the targets are readily accessible on the outside where teixobactin binds precursors of peptidoglycan (PG) and WTA. CM, cytoplasmic membrane; CW, cell wall; OM, outer membrane; T, teixobactin. (Credit: Nature. 2015. 517:455-459).

2015 in Review #2: Cholesterol-lowering drugs

Efficacy and Safety of Alirocumab in Reducing Lipids and Cardiovascular Events

Journal: The New England Journal of Medicine • Authors: Jennifer G. Robinson and Colleagues • Institution: ODYSSEY LONG TERM Investigators

2015 in Review #2: Cholesterol-lowering drugs

Efficacy and Safety of Alirocumab in Reducing Lipids and Cardiovascular Events

Journal: The New England Journal of Medicine • Authors: Jennifer G. Robinson and Colleagues • Institution: ODYSSEY LONG TERM Investigators

2015 in Review #2: Cholesterol-lowering drugs

Efficacy and Safety of Alirocumab in Reducing Lipids and Cardiovascular Events
Journal: The New England Journal of Medicine • Authors: Jennifer G. Robinson and Colleagues • Institution: ODYSSEY LONG TERM Investigators

2015 in Review #2: Cholesterol-lowering drugs

Efficacy and Safety of Alirocumab in Reducing Lipids and Cardiovascular Events
Journal: The New England Journal of Medicine • Authors: Jennifer G. Robinson and Colleagues • Institution: ODYSSEY LONG TERM Investigators

High blood cholesterol is a major risk factor for heart disease. Early phase clinical studies have shown that inhibition of the proprotein convertase subtilisin/kexin type 9 (PCSK9) by a monoclonal antibody, Alirocumab, reduces blood cholesterol levels in patients. Dr. Robinson et al (2015) published an article in the March issue of the New England Journal of Medicine describing their phase 3, randomized, double-blind, placebo-controlled trial with 2,341 high blood cholesterol patients (2). Their study proves that Alirocumab significantly reduced blood cholesterol levels over a period of 78 weeks. The U.S. Food and Drug Administration subsequently approved Alirocumab to treat qualifying patients with high cholesterol (3). Additionally, cholesterol-lowering effects of another antibody against PCSK9, Evolocumab, were reported in the same March, 2015 issue of the New England Journal of Medicine (4). While this is an impactful study, it is worth noting that it remains unclear whether Alirocumab can improve health outcomes of cardiovascular disease.

  1. Efficacy and Safety of Alirocumab in Reducing Lipids and Cardiovascular Events [2015-04-16; Jennifer G. Robinson, M.D., M.P.H., Michel Farnier, M.D., Ph.D., Michel Krempf, M.D., Jean Bergeron, M.D., Gérald Luc, M.D., Maurizio Averna, M.D., Erik S. Stroes, M.D., Ph.D., Gisle Langslet, M.D., Frederick J. Raal, M.D., Ph.D., Mahfouz El Shahawy, M.D., Michael J. Koren, M.D., Norman E. Lepor, M.D., Christelle Lorenzato, M.Sc., Robert Pordy, M.D., Umesh Chaudhari, M.D., and John J.P. Kastelein, M.D., Ph.D., for the ODYSSEY LONG TERM Investigators, N Engl J Med 2015; 372:1489-1499 |April 16, 2015| DOI: 10.1056/NEJMoa1501031]
  2. FDA approves Praluent to treat certain patients with high cholesterol [2015-07-24; U.S. Food & Drug Administration]
  3. Efficacy and Safety of Evolocumab in Reducing Lipids and Cardiovascular Events [2015-04-06; Marc S. Sabatine, M.D., M.P.H., Robert P. Giugliano, M.D., Stephen D. Wiviott, M.D., Frederick J. Raal, M.B., B.Ch., M.Med., Ph.D., Dirk J. Blom, M.B., Ch.B., M.Med., Ph.D., Jennifer Robinson, M.D., M.P.H., Christie M. Ballantyne, M.D., Ransi Somaratne, M.D., Jason Legg, Ph.D., Scott M. Wasserman, M.D., Robert Scott, M.D., Michael J. Koren, M.D., and Evan A. Stein, M.D., Ph.D., for the Open-Label Study of Long-Term Evaluation against LDL Cholesterol (OSLER) Investigators, N Engl J Med. 2015 Apr 16;372(16):1500-9. doi: 10.1056/NEJMoa1500858]
2015 in Review #2: Cholesterol-lowering drugs

Calculated LDL Cholesterol Levels over Time (Intention-to-Treat Analysis)
Left axis: milligrams per deciliter. Right axis: millimoles per liter.

Values above the data points indicate least-squares mean absolute LDL cholesterol levels, and values below the data points indicate least-squares mean percentage changes from baseline. Values below the chart indicate the number of patients with LDL cholesterol values available for the intention-to-treat analysis at each time point; these include levels measured while the study drug was being taken and, in the case of patients who discontinued the study drug but returned to the clinic for assessments, after the study drug was discontinued. Missing data were accounted for with the use of a mixed-effects model with repeated measures. For statin therapy, the maximum tolerated dose was the highest dose associated with an acceptable side-effect profile. LLT denotes lipid-lowering therapy. (Credit: The New England Journal of Medicine).

2015 in Review #2: Cholesterol-lowering drugs

Calculated LDL Cholesterol Levels over Time (Intention-to-Treat Analysis)
Left axis: milligrams per deciliter. Right axis: millimoles per liter.

Values above the data points indicate least-squares mean absolute LDL cholesterol levels, and values below the data points indicate least-squares mean percentage changes from baseline. Values below the chart indicate the number of patients with LDL cholesterol values available for the intention-to-treat analysis at each time point; these include levels measured while the study drug was being taken and, in the case of patients who discontinued the study drug but returned to the clinic for assessments, after the study drug was discontinued. Missing data were accounted for with the use of a mixed-effects model with repeated measures. For statin therapy, the maximum tolerated dose was the highest dose associated with an acceptable side-effect profile. LLT denotes lipid-lowering therapy. (Credit: The New England Journal of Medicine).

2015 in Review #2: Cholesterol-lowering drugs

Calculated LDL Cholesterol Levels over Time
(Intention-to-Treat Analysis)
Left axis: milligrams per deciliter.
Right axis: millimoles per liter.

Values above the data points indicate least-squares mean absolute LDL cholesterol levels, and values below the data points indicate least-squares mean percentage changes from baseline. Values below the chart indicate the number of patients with LDL cholesterol values available for the intention-to-treat analysis at each time point; these include levels measured while the study drug was being taken and, in the case of patients who discontinued the study drug but returned to the clinic for assessments, after the study drug was discontinued. Missing data were accounted for with the use of a mixed-effects model with repeated measures. For statin therapy, the maximum tolerated dose was the highest dose associated with an acceptable side-effect profile. LLT denotes lipid-lowering therapy. (Credit: The New England Journal of Medicine).

2015 in Review #2: Cholesterol-lowering drugs

Calculated LDL Cholesterol Levels over Time (Intention-to-Treat Analysis)
Left axis: milligrams per deciliter.
Right axis: millimoles per liter.

Values above the data points indicate least-squares mean absolute LDL cholesterol levels, and values below the data points indicate least-squares mean percentage changes from baseline. Values below the chart indicate the number of patients with LDL cholesterol values available for the intention-to-treat analysis at each time point; these include levels measured while the study drug was being taken and, in the case of patients who discontinued the study drug but returned to the clinic for assessments, after the study drug was discontinued. Missing data were accounted for with the use of a mixed-effects model with repeated measures. For statin therapy, the maximum tolerated dose was the highest dose associated with an acceptable side-effect profile. LLT denotes lipid-lowering therapy. (Credit: The New England Journal of Medicine).

2015 in Review #3: Bioengineering

A technology platform to assess multiple cancer agents simultaneously within a patient’s tumor

Journal: Science Translational Medicine • Authors: Richard A. Klinghoffer and Colleagues • Institutions: Seattle, WA : Presage Biosciences; Clinical Research Division, Fred Hutchinson Cancer Research Center; Oncology Department, BluePearl Veterinary Partners; Department of Pediatrics, University of Washington; Seattle Children’s Hospital. San Francisco, CA : Celgene Corporation. Summit, NJ : Celgene Corporation.

2015 in Review #3: Bioengineering

A technology platform to assess multiple cancer agents simultaneously within a patient’s tumor

Journal: Science Translational Medicine • Authors: Richard A. Klinghoffer and Colleagues • Institutions: Seattle, WA : Presage Biosciences; Clinical Research Division, Fred Hutchinson Cancer Research Center; Oncology Department, BluePearl Veterinary Partners; Department of Pediatrics, University of Washington; Seattle Children’s Hospital. San Francisco, CA : Celgene Corporation. Summit, NJ : Celgene Corporation.

2015 in Review #3: Bioengineering

A technology platform to assess multiple cancer agents simultaneously within a patient’s tumor
Journal: Science Translational Medicine • Authors: Richard A. Klinghoffer and Colleagues • Institutions: Seattle, WA : Presage Biosciences; Clinical Research Division, Fred Hutchinson Cancer Research Center; Oncology Department, BluePearl Veterinary Partners; Department of Pediatrics, University of Washington; Seattle Children’s Hospital. San Francisco, CA : Celgene Corporation. Summit, NJ : Celgene Corporation.

2015 in Review #3: Bioengineering

A technology platform to assess multiple cancer agents simultaneously within a patient’s tumor
Journal: Science Translational Medicine • Authors: Richard A. Klinghoffer and Colleagues • Institutions: Seattle, WA : Presage Biosciences; Clinical Research Division, Fred Hutchinson Cancer Research Center; Oncology Department, BluePearl Veterinary Partners; Department of Pediatrics, University of Washington; Seattle Children’s Hospital. San Francisco, CA : Celgene Corporation. Summit, NJ : Celgene Corporation.

Despite advances in cancer drug treatment, individual patient response still complicates the process of choosing an effective cancer treatment. However, research published in the April 2015 publication of Science Translational Medicine offers possible answers to this problem. A tumor-implantable drug delivery medical device called CIVO was developed to introduce multiple drugs into specific locations of tumor sites in mice, dogs, and humans (5). Further studies show that the CIVO platform predicts outcomes of systemically delivered drugs in animals, screened effective cancer drugs, and induced anti-cancer responses within specific tumor sites. That is to say, the CIVO technology could be utilized to test multiple drugs in an individual cancer patient, determining the efficacy of a particular treatment for a specific patient. Yet another study in the same issue of Science Translational Medicine describes an implantable micro-device which offers another method to test the effectiveness of drugs in tumor sites (6).

  1. A technology platform to assess multiple cancer agents simultaneously within a patient’s tumor [2015-04-22; Richard A. Klinghoffer, S. Bahram Bahrami, Beryl A. Hatton, Jason P. Frazier, Alicia Moreno-Gonzalez, Andrew D. Strand, William S. Kerwin, Joseph R. Casalini, Derek J. Thirstrup, Sheng You, Shelli M. Morris, Korashon L. Watts, Mandana Veiseh, Marc O. Grenley, Ilona Tretyak, Joyoti Dey, Michael Carleton, Emily Beirne, Kyle D. Pedro, Sally H. Ditzler, Emily J. Girard, Thomas L. Deckwerth, Jessica A. Bertout, Karri A. Meleo, Ellen H. Filvaroff, Rajesh Chopra, Oliver W. Press and James M. Olson, Science Translational Medicine 22 Apr 2015: Vol. 7, Issue 284, pp. 284ra57 | DOI: 10.1126/scitranslmed.3010564]
  2. An implantable microdevice to perform high-throughput in vivo drug sensitivity testing in tumors [2015-04-22; Oliver Jonas, Heather M. Landry, Jason E. Fuller, John T. Santini Jr., Jose Baselga, Robert I. Tepper, Michael J. Cima and Robert Langer – Science Translational Medicine 22 Apr 2015: Vol. 7, Issue 284, pp. 284ra57 | DOI: 10.1126/scitranslmed.3010564]
2015 in Review #3: Bioengineering

The CIVO tumor microinjection platform

(A) The CIVO platform consists of a handheld array of up to eight needles capable of simultaneously penetrating subcutaneous tumors and delivering microdoses of candidate therapeutics. (B) For preclinical studies, tumors were grown as flank xenografts in immunocompromised mice and injected while mice were anesthetized. A chemically inert ITD was co-injected through each needle. (C) A representative example of the ITD signal from a tumor injected using a five-needle array visualized with a Xenogen In Vivo Imaging System (IVIS). (D) A longitudinal IVIS scan demonstrating the column-like distribution of the tracking dye signal from a single needle spanning the z axis of the tumor. (E) Tumor responses were assessed after resection of the tumor via histological staining of cross sections (4 μm thick) sampled at 2-mm intervals perpendicular to the injection column. (F) High-resolution whole-slide scanning captured images of every cell from each 4-μm-thick tissue section. (G) A representative tumor response to microinjected drug at a single injection site. Nuclei, DAPI (4′,6-diamidino-2-phenylindole) (blue); ITD (green); a drug-specific biomarker (orange). (H) The resulting images were processed by a custom image analysis platform called CIVO Analyzer, which classifies the cells within each region of interest as biomarker-positive (green dots) or biomarker-negative (red dots). (Credit: Science Translational Medicine).

2015 in Review #3: Bioengineering

The CIVO tumor microinjection platform

(A) The CIVO platform consists of a handheld array of up to eight needles capable of simultaneously penetrating subcutaneous tumors and delivering microdoses of candidate therapeutics. (B) For preclinical studies, tumors were grown as flank xenografts in immunocompromised mice and injected while mice were anesthetized. A chemically inert ITD was co-injected through each needle. (C) A representative example of the ITD signal from a tumor injected using a five-needle array visualized with a Xenogen In Vivo Imaging System (IVIS). (D) A longitudinal IVIS scan demonstrating the column-like distribution of the tracking dye signal from a single needle spanning the z axis of the tumor. (E) Tumor responses were assessed after resection of the tumor via histological staining of cross sections (4 μm thick) sampled at 2-mm intervals perpendicular to the injection column. (F) High-resolution whole-slide scanning captured images of every cell from each 4-μm-thick tissue section. (G) A representative tumor response to microinjected drug at a single injection site. Nuclei, DAPI (4′,6-diamidino-2-phenylindole) (blue); ITD (green); a drug-specific biomarker (orange). (H) The resulting images were processed by a custom image analysis platform called CIVO Analyzer, which classifies the cells within each region of interest as biomarker-positive (green dots) or biomarker-negative (red dots). (Credit: Science Translational Medicine).

2015 in Review #3: Bioengineering

The CIVO tumor microinjection platform

(A) The CIVO platform consists of a handheld array of up to eight needles capable of simultaneously penetrating subcutaneous tumors and delivering microdoses of candidate therapeutics. (B) For preclinical studies, tumors were grown as flank xenografts in immunocompromised mice and injected while mice were anesthetized. A chemically inert ITD was co-injected through each needle. (C) A representative example of the ITD signal from a tumor injected using a five-needle array visualized with a Xenogen In Vivo Imaging System (IVIS). (D) A longitudinal IVIS scan demonstrating the column-like distribution of the tracking dye signal from a single needle spanning the z axis of the tumor. (E) Tumor responses were assessed after resection of the tumor via histological staining of cross sections (4 μm thick) sampled at 2-mm intervals perpendicular to the injection column. (F) High-resolution whole-slide scanning captured images of every cell from each 4-μm-thick tissue section. (G) A representative tumor response to microinjected drug at a single injection site. Nuclei, DAPI (4′,6-diamidino-2-phenylindole) (blue); ITD (green); a drug-specific biomarker (orange). (H) The resulting images were processed by a custom image analysis platform called CIVO Analyzer, which classifies the cells within each region of interest as biomarker-positive (green dots) or biomarker-negative (red dots). (Credit: Science Translational Medicine).

2015 in Review #3: Bioengineering

The CIVO tumor microinjection platform

(A) The CIVO platform consists of a handheld array of up to eight needles capable of simultaneously penetrating subcutaneous tumors and delivering microdoses of candidate therapeutics. (B) For preclinical studies, tumors were grown as flank xenografts in immunocompromised mice and injected while mice were anesthetized. A chemically inert ITD was co-injected through each needle. (C) A representative example of the ITD signal from a tumor injected using a five-needle array visualized with a Xenogen In Vivo Imaging System (IVIS). (D) A longitudinal IVIS scan demonstrating the column-like distribution of the tracking dye signal from a single needle spanning the z axis of the tumor. (E) Tumor responses were assessed after resection of the tumor via histological staining of cross sections (4 μm thick) sampled at 2-mm intervals perpendicular to the injection column. (F) High-resolution whole-slide scanning captured images of every cell from each 4-μm-thick tissue section. (G) A representative tumor response to microinjected drug at a single injection site. Nuclei, DAPI (4′,6-diamidino-2-phenylindole) (blue); ITD (green); a drug-specific biomarker (orange). (H) The resulting images were processed by a custom image analysis platform called CIVO Analyzer, which classifies the cells within each region of interest as biomarker-positive (green dots) or biomarker-negative (red dots). (Credit: Science Translational Medicine).

2015 in Review #4: Link between brain and immune system

Structural and functional features of central nervous system lymphatic vessels.

Journal: Nature • Authors: Antoine Louveau and Colleagues • Institution: School of Medicine of the University of Virginia: Center for Brain Immunology and Glia, Department of Neuroscience, Department of Neurosurgery, Beirne B. Carter Center for Immunology Research, Department of Medicine (Division of Allergy), Department of Microbiology, Immunology, and Cancer Biology, Department of Cell Biology, Department of Pathology (Neuropathology), Medical Scientist Training Program.

2015 in Review #4: Link between brain and immune system

Structural and functional features of central nervous system lymphatic vessels.

Journal: Nature • Authors: Antoine Louveau and Colleagues • Institution: School of Medicine of the University of Virginia: Center for Brain Immunology and Glia, Department of Neuroscience, Department of Neurosurgery, Beirne B. Carter Center for Immunology Research, Department of Medicine (Division of Allergy), Department of Microbiology, Immunology, and Cancer Biology, Department of Cell Biology, Department of Pathology (Neuropathology), Medical Scientist Training Program.

2015 in Review #4: Link between brain and immune system

Structural and functional features of central nervous system lymphatic vessels.
Journal: Nature • Authors: Antoine Louveau and Colleagues • Institution: School of Medicine of the University of Virginia: Center for Brain Immunology and Glia, Department of Neuroscience, Department of Neurosurgery, Beirne B. Carter Center for Immunology Research, Department of Medicine (Division of Allergy), Department of Microbiology, Immunology, and Cancer Biology, Department of Cell Biology, Department of Pathology (Neuropathology), Medical Scientist Training Program.

2015 in Review #4: Link between brain and immune system

Structural and functional features of central nervous system lymphatic vessels.
Journal: Nature • Authors: Antoine Louveau and Colleagues • Institution: School of Medicine of the University of Virginia: Center for Brain Immunology and Glia, Department of Neuroscience, Department of Neurosurgery, Beirne B. Carter Center for Immunology Research, Department of Medicine (Division of Allergy), Department of Microbiology, Immunology, and Cancer Biology, Department of Cell Biology, Department of Pathology (Neuropathology), Medical Scientist Training Program.

A January 2015 article published in Nature contests information once accepted as certainty (7). Decades of immunology textbooks maintain that the central nervous system lacks a classical lymphatic drainage system. However, a rigorous study clearly shows the presence of a functional and classical lymphatic system within the central nervous system. Another study published in the Journal of Experimental Medicine in June of 2015 confirms the discovery (8). Of interests to scientists is the involvement of this lymphatic system in the pathogenesis of neurological disorders such as multiple sclerosis, Alzheimer’s disease, and meningitis.

  1. Structural and functional features of central nervous system lymphatic vessels [2015-07-16; Antoine Louveau, Igor Smirnov, Timothy J. Keyes, Jacob D. Eccles, Sherin J. Rouhani, J. David Peske, Noel C. Derecki, David Castle, James W. Mandell, S. Lee Kevin, Tajie H. Harris, and Jonathan Kipnis, Nature. 2015 Jul 16;523(7560):337-41. doi: 10.1038/nature14432. Epub 2015 Jun 1.]
  2. A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules [2015-06-29; Aleksanteri Aspelund, Salli Antila, Steven T. Proulx, Tine Veronica Karlsen, Sinem Karaman, Michael Detmar, Helge Wiig, and Kari Alitalo, Journal of Experimental Medicine. 2015 Jun 29;212(7):991-9. doi: 10.1084/jem.20142290. Epub 2015 Jun 15.]
2015 in Review #4: Link between Brain and Immune System

Lymphatic Vessel Network in the Meningeal Linings of the Brain

A schematic image of the novel lymphatic vessel network in the meningeal linings of the brain, discovered by Aleksanteri Aspelund and collaborators. (A) Previously, lymphatic vessels in the nasal mucosa were known to drain cerebrospinal fluid, but it was thoughts that the lymphatic vessels did not extend into the brain. (B-C) The new findings revealed that the dura mater lymphatic system is important for the drainage of brain interstitial fluid, macromolecules and cerebrospinal fluid. (Credit: Kari Alitalo, Wihuri Research Institute / Translational Cancer Biology Program, University of Helsinski).

2015 in Review #4: Link between Brain and Immune System

Lymphatic Vessel Network in the Meningeal Linings of the Brain

A schematic image of the novel lymphatic vessel network in the meningeal linings of the brain, discovered by Aleksanteri Aspelund and collaborators. (A) Previously, lymphatic vessels in the nasal mucosa were known to drain cerebrospinal fluid, but it was thoughts that the lymphatic vessels did not extend into the brain. (B-C) The new findings revealed that the dura mater lymphatic system is important for the drainage of brain interstitial fluid, macromolecules and cerebrospinal fluid. (Credit: Kari Alitalo, Wihuri Research Institute / Translational Cancer Biology Program, University of Helsinski).

2015 in Review #4: Link between Brain and Immune System

Lymphatic Vessel Network in the Meningeal Linings of the Brain

A schematic image of the novel lymphatic vessel network in the meningeal linings of the brain, discovered by Aleksanteri Aspelund and collaborators. (A) Previously, lymphatic vessels in the nasal mucosa were known to drain cerebrospinal fluid, but it was thoughts that the lymphatic vessels did not extend into the brain. (B-C) The new findings revealed that the dura mater lymphatic system is important for the drainage of brain interstitial fluid, macromolecules and cerebrospinal fluid. (Credit: Kari Alitalo, Wihuri Research Institute / Translational Cancer Biology Program, University of Helsinski).

2015 in Review #4: Link between Brain and Immune System

Lymphatic Vessel Network in the Meningeal Linings of the Brain

A schematic image of the novel lymphatic vessel network in the meningeal linings of the brain, discovered by Aleksanteri Aspelund and collaborators. (A) Previously, lymphatic vessels in the nasal mucosa were known to drain cerebrospinal fluid, but it was thoughts that the lymphatic vessels did not extend into the brain. (B-C) The new findings revealed that the dura mater lymphatic system is important for the drainage of brain interstitial fluid, macromolecules and cerebrospinal fluid. (Credit: Kari Alitalo, Wihuri Research Institute / Translational Cancer Biology Program, University of Helsinski).

2015 in Review #5: Kennewick Man

Kennewick Man is an 8,500 skeleton discovered in Washington State. Although he was discovered in 1996 he is generating renewed scientific debate due to a recent human genetic study published in the June 2015 publication of Nature. The study presents Kennewick Man’s autosomal DNA, mitochondrial DNA and Y chromosome data as proof that Kennewick Man is more closely related to Native North Americans than to any other population in the world (9). Kennewick Man does retain some mystery; the absence of a comprehensive comparative DNA database of modern Native American groups prevents scientists from uncovering the Native American group to which Kennewick Man is mostly closely related.

  1. Morten Rasmussen, et al. The ancestry and affiliations of Kennewick Man. Nature. 523:455-458.
2015 in Review #5: Kennewick Man

2015 in Review #5: Kennewick Man

2015 in Review #5: Kennewick Man

2015 in Review #5: Kennewick Man

2015 in Review #5: Kennewick Man

2015 in Review #5: Kennewick Man

2015 in Review #5: Kennewick Man

2015 in Review #5: Kennewick Man

2015 in Review #6: Ebola vaccine

Over the last two years West Africa, along with several other affected countries, has experienced the most widespread epidemic of Ebola in history. Dr. Henao-Restrepo et al (2015) addressed this urgent need for an Ebola vaccine in an open-label, cluster-randomized phase 3 trial of a vesicular stomatitis virus-based Ebola vaccine. Their vaccine was administered through a ring vaccination strategy; that is, vaccinating a cluster of people either socially or geographically connected with a confirmed patient. The interim results were published in the Lancet’s July 2015 publication, indicating that the vaccine has the potential to be both safe and highly effective in preventing Ebola (10). The authors point out that the continued enrollment, vaccination, and follow-up would provide additional evidence of the vaccine’s efficacy in preventing Ebola. Further successful results over time have the potential to inform policy and regulatory changes in the Ebola vaccination strategy. Additionally, it was reported in the August 2015 publication of Science that the similar vesicular stomatitis virus-based Ebola vaccine is shown to rapidly protect macaques against Ebola infection (11).

  1. Ana Maria Henao-Restrepo, et al. Efficacy and effectiveness of an rVSV-vectored vaccine expressing Ebola surface glycoprotein: interim results from the Guinea ring vaccination cluster-randomised trial. Lancet. 2015. 380:858-866.
  2. Andrea Marzi, et al. VSV-EBOV rapidly protects macaques against infection with the 2014/15 Ebola virus outbreak strain. Science 2015. 349:739-742.
2015 in Review #6: Ebola Vaccine

2015 in Review #6: Ebola vaccine

2015 in Review #6: Ebola Vaccine

2015 in Review #6: Ebola vaccine

2015 in Review #6: Ebola Vaccine

2015 in Review #6: Ebola vaccine

2015 in Review #6: Ebola Vaccine

2015 in Review #6: Ebola vaccine

2015 in Review #7: Biomaterials

Many medical devices have been designed and used to improve the independence and the mobility of disabled individuals. A primary challenge in advancing these devices is the difficulty in adding tactile sensing that mimics human skins’ sensory system which send signals for pain, touch or temperature to the nervous system. Dr. Bao et al (2015) designed a sensory system, skin-inspired organic digital mechanoreceptor, and published their study in the August 2015 issue of Science. Their sensory system can feel pressure, then generating and transmitting digital signals to the brain’s neuron cells (12). Although the research thus far has been in an in vitro mouse tissue model, this system has the potential to propel design in highly functional prosthetics.

  1. Benjamin C.-K. Tee, et al. A skin-inspired organic digital mechanoreceptor. Science. 2015. 350:313-316.
2015 in Review #7: Biomaterials

2015 in Review #7: Biomaterials

2015 in Review #7: Biomaterials

2015 in Review #7: Biomaterials

2015 in Review #7: Biomaterials

2015 in Review #7: Biomaterials

2015 in Review #7: Biomaterials

2015 in Review #7: Biomaterials

2015 in Review #8: Synthetic biology

Opioids act on the nervous system and are primarily used in pain management and specialized care for people with serious disease. At present the sole source of opioids is the poppy farming industry but an alternative may soon be available. According to a report published in the August 2015 issue of Science, Stanford scientists have engineered yeast to complete biosynthesis of opioids (through a comprehensive genetic design and optimization of cultivation conditions) in a biosafety laboratory (13). Although there are hurdles to overcome first, the industrialization of this technology has the potential to create an alternative opioid supplier.

  1. Stephanie Galanie, et al. Complete biosynthesis of opioids in yeast. Science. 2015. 349:1095-1100.
2015 in Review #8: Synthetic biology

2015 in Review #8: Synthetic biology

2015 in Review #8: Synthetic biology

2015 in Review #8: Synthetic biology

2015 in Review #8: Synthetic biology

2015 in Review #8: Synthetic biology

2015 in Review #8: Synthetic biology

2015 in Review #8: Synthetic biology

2015 in Review #9: Immunotherapy

According to an article published in the New England Journal of Medicine in September of 2015, treatment with an anti-PD-1 antibody, Nivolumab, in patients with advanced nonsquamous non-small-cell lung cancer has improved the overall survival compared to that with the chemotherapy drug, Docetaxel. The article is a result of a randomized, open-label, international phase 3 trial (14). PD-1 functions as an immune checkpoint to prevent T cell activation and down-regulate the immune system. Blocking the PD-1 pathway has exhibited activation of the immune system against cancer. In fact, just a few months before the publication of the 2015 journal article the U.S. Food and Drug Administration approved Nivolumab to treat patients with squamous non-small cell lung cancer with progression on or after platinum -based chemotherapy (15).

  1. Hossein Borghaei, et al. Nivolumab versus Docetaxel in advanced nonsquamous non-small-cell lung cancer. New England Journal of Medicine. 2015. 373:1627-1639.
  2. Approved drug: Nivolumab (Opdivo). March 4, 2015.
2015 in Review #9: Immunotherapy

2015 in Review #9: Immunotherapy

2015 in Review #9: Immunotherapy

2015 in Review #9: Immunotherapy

2015 in Review #9: Immunotherapy

2015 in Review #9: Immunotherapy

2015 in Review #9: Immunotherapy

2015 in Review #9: Immunotherapy

2015 in Review #10: CRISPR-Cas9-mediated genome editing

CRISPR-Cas9 is a gene-editing technology that targets and modifies the genome, holding the potential to treat genetic diseases through gene corrections. However, it remains unclear whether this technology can correct gene mutations in post-mitotic adult tissues (e.g. skeletal muscles or the heart). In the December 2015 issue of Science a group of University of Texas Southwestern Medical Center researchers addressed this gene editing technology. The team developed an adeno-associated virus-9 based CRISPR/Cas9 genomic editing system to correct mutations in Muscular Dystrophy (16); their study shows that the application of this system partially restores dystropin expression in skeletal and cardia muscles, resulting in enhanced muscle function. Due to the lack of comprehensive and unbiased analysis of any abnormalities in the mouse genome following application of the system safety concerns must be addressed. Nevertheless, this newly developed genomic editing system is an important prospect in the future of correcting mutations in post-mitotic adult tissues with human Duchenne Muscular Dystrophy. Two additional studies published in the same issue of Science offer similar findings (17, 18).

  1. Chengzu Long, et al. Postnatal genome editing partially restores dystrophin expression in a mouse model of muscular dystrophy. Science. Published online December 31, 2015.
  2. Mohammadsharif Tabebordbar, et al. In vivo gene editing in dystrophic mouse muscle and muscle stem cells. Science. Published online December 31, 2015.
  3. Christopher E. Nelson, et al. In vivo genome editing improves muscle function in a mouse model of Duchenne muscular dystrophy. Science. Published online December 31, 2015.
2015 in Review #10: CRISPR-Cas9-mediated genome editing

2015 in Review #10: CRISPR-Cas9-mediated genome editing

2015 in Review #10: CRISPR-Cas9-mediated genome editing

2015 in Review #10: CRISPR-Cas9-mediated genome editing

2015 in Review #10: CRISPR-Cas9-mediated genome editing

2015 in Review #10: CRISPR-Cas9-mediated genome editing

2015 in Review #10: CRISPR-Cas9-mediated genome editing

2015 in Review #10: CRISPR-Cas9-mediated genome editing

Credit: English Text curated by Jinnah Griffin

Wanqiu Hou is the Founder of Scientific HealthSense, a website based application in mining health data for a consumer service. He received his PhD from the Chinese Academy of Sciences. Dr. Hou has more than 10 years of experience in medical research, writing and communications.

Wanqiu Hou is the Founder of Scientific HealthSense, a website based application in mining health data for a consumer service. He received his PhD from the Chinese Academy of Sciences. Dr. Hou has more than 10 years of experience in medical research, writing and communications.

Wanqiu Hou is the Founder of Scientific HealthSense, a website based application in mining health data for a consumer service. He received his PhD from the Chinese Academy of Sciences. Dr. Hou has more than 10 years of experience in medical research, writing and communications.

Wanqiu Hou is the Founder of Scientific HealthSense, a website based application in mining health data for a consumer service. He received his PhD from the Chinese Academy of Sciences. Dr. Hou has more than 10 years of experience in medical research, writing and communications.


The Michelson Medical Research Foundation's Groundwork blog is brought to you thanks to the generous support of Dr. Gary K. Michelson and his wife, Alya Michelson.

The Michelson Medical Research Foundation's Groundwork blog is brought to you thanks to the generous support of Dr. Gary K. Michelson and his wife, Alya Michelson.

The Michelson Medical Research Foundation's Groundwork blog is brought to you thanks to the generous support of Dr. Gary K. Michelson and his wife, Alya Michelson.

The Michelson Medical Research Foundation's Groundwork blog is brought to you thanks to the generous support of Dr. Gary K. Michelson and his wife, Alya Michelson.